WO2024258866A1 - Compositions et procédés pour le traitement de troubles immunologiques - Google Patents

Compositions et procédés pour le traitement de troubles immunologiques Download PDF

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WO2024258866A1
WO2024258866A1 PCT/US2024/033431 US2024033431W WO2024258866A1 WO 2024258866 A1 WO2024258866 A1 WO 2024258866A1 US 2024033431 W US2024033431 W US 2024033431W WO 2024258866 A1 WO2024258866 A1 WO 2024258866A1
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sequence
amino acid
acid sequence
protein
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Philip R. Johnson
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Interius Biotherapeutics Inc
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Interius Biotherapeutics Inc
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Priority to KR1020267001021A priority Critical patent/KR20260025141A/ko
Priority to AU2024303971A priority patent/AU2024303971A1/en
Priority to CN202480045904.8A priority patent/CN121487755A/zh
Priority to IL325221A priority patent/IL325221A/en
Priority to EP24824015.2A priority patent/EP4724112A1/fr
Priority to JP2025572326A priority patent/JP2026521514A/ja
Publication of WO2024258866A1 publication Critical patent/WO2024258866A1/fr
Priority to MX2025015011A priority patent/MX2025015011A/es
Anticipated expiration legal-status Critical
Priority to CONC2025/0018255A priority patent/CO2025018255A2/es
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    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
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    • A61K40/00—Cellular immunotherapy
    • A61K40/10—Cellular immunotherapy characterised by the cell type used
    • A61K40/13—B-cells
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    • A61K40/30—Cellular immunotherapy characterised by the recombinant expression of specific molecules in the cells of the immune system
    • A61K40/31—Chimeric antigen receptors [CAR]
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    • A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41—Vertebrate antigens
    • A61K40/42—Cancer antigens
    • A61K40/4202—Receptors, cell surface antigens or cell surface determinants
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
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    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2887—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD20
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K2239/10—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterized by the structure of the chimeric antigen receptor [CAR]
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    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the cancer treated
    • A61K2239/48—Blood cells, e.g. leukemia or lymphoma
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    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
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    • C07K2319/00—Fusion polypeptide
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    • C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
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    • C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
    • C12N2740/15041—Use of virus, viral particle or viral elements as a vector
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Definitions

  • FIELD Embodiments provided herein relate to viral particles comprising a heterologous viral glycoprotein and a targeting moiety having the formula T-S1, wherein T is a target binding domain and S1 is a stalk portion.
  • the stalk portion may comprise variant Fc domains.
  • the stalk portion may comprise a flexible peptide domain.
  • the viral particle may further comprise a nucleic acid molecule encoding for a heterologous molecule of interest.
  • the heterologous molecule of interest may be useful in the treatment of a disease or disorder, such as but not limited to an immunological disorder.
  • Embodiments provided herein further relate to compositions comprising the viral particles provided for herein and methods of using the same.
  • BACKGROUND Vesicular stomatitis virus (VSV) is an enveloped, negative-strand RNA virus that belongs to the Vesiculovirus genus of the Rhabdovirus family. It is an arbovirus which can infect insects, cattle, horses and pigs.
  • the VSV genome encodes five structural proteins, among which a single transmembrane glycoprotein (G).
  • G transmembrane glycoprotein
  • the glycoprotein is a classic type I membrane glycoprotein with an amino-terminal signal peptide, an ectodomain of about 450 amino acids, a single alpha helical transmembrane segment and a small intraviral carboxy-terminal domain.
  • the signal peptide is cleaved in the lumen of the endoplasmic reticulum, and the native mature glycoprotein consists of the ectodomain, the transmembrane domain and the intraviral domain.
  • G plays a critical role during the initial steps of virus infection (Albertini, A. A. V., Baquero, E., Ferlin, A., and Gaudin, Y. (2012). Molecular and Cellular Aspects of Rhabdovirus Entry. Viruses 4, 117-139.), which is hereby incorporated by reference in its entirety. First, it is responsible for virus attachment to specific receptors.
  • virions enter the cell by IPTS/128579164.3 DOCKET NO: INH-029WO PATENT a clathrin-mediated endocytic pathway.
  • G triggers the fusion between the viral and endosomal membranes, which releases the genome in the cytosol for the subsequent steps of infection. Fusion is catalyzed by a low-pH-induced large structural transition from a pre-toward a post-fusion conformation which are both trimeric (Roche, S., Bressanelli, S., Rey, F. A., and Gaudin, Y. (2006).
  • LDL-R low-density lipoprotein receptor
  • VSV receptors Flinkelshtein, D., Werman, A., Novick, D., Barak, S., and Rubinstein, M. (2013).
  • LDL receptor and its family members serve as the cellular receptors for vesicular stomatitis virus.
  • VSV-G can be used for pseudotyping other viruses and VSV-G- pseudotyped lentiviruses (VSV-G-LVs) exhibit the same broad tropism as VSV. However, this broad tropism can inhibit the selective targeting of specific cell types. Therefore, there is a need, for modified (mutated or mutant) VSV-G proteins that can be used to pseudotype viruses that abrogate its binding to the LDL receptor. The present embodiments, fulfill these needs as well as others. BRIEF SUMMARY In some embodiments, a viral particle is provided.
  • the viral particle comprises a heterologous viral glycoprotein and a targeting moiety wherein the targeting moiety comprises a polypeptide having the formula T-S1, wherein T is a target binding domain and S1 is a stalk portion.
  • the stalk portion S1 comprises variant Fc protein.
  • the variant Fc protein comprises a transmembrane domain, such as, but not -2- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT limited to, a CD8 or CD28 transmembrane domain.
  • the variant Fc protein comprises an effector mutation, wherein the effector mutation inhibits the interaction between the Fc protein and a Fc interacting protein, such as Fc ⁇ R, C1q, FcR ⁇ , or FcRn.
  • the variant Fc protein is a variant IgG1 Fc protein comprising one or more mutations selected from the group consisting of : L234A, L235A, N297A, P329G, I253A, H310A, and H435A.
  • the variant IgG1 Fc protein comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 104, at least 85% identity to SEQ ID NO: 104, at least 90% identity to SEQ ID NO: 104, at least 95% identity to SEQ ID NO: 104, at least 98% identity to SEQ ID NO: 104, or at least 100% identity to SEQ ID NO: 104.
  • the variant Fc protein is a variant IgG2 Fc protein comprising one or more mutations selected from the group consisting of: N297A, P329G, I253A, H310A, and H435A.
  • the variant Fc protein is a variant IgG4 Fc protein comprising one or more mutations selected from the group consisting of: S228P, L235E, N297A, P329G, I253A, H310A, and H435A.
  • the targeting moiety having the formula T-S1 comprises a stalk portion S1 having a formula of L1-Fc-L2-X1, wherein L1 is a linker or absent, Fc is a variant Fc protein, L2 is a linker or absent, and X1 is a polypeptide comprising the transmembrane domain, wherein the targeting moiety having the formula T-S1 has a formula of T-L1-Fc-L2-X1.
  • the polypeptide comprising the transmembrane domain (X1) comprises a polypeptide having a formula of ECD-TM-ICD, wherein ECD is an extracellular domain, or a fragment thereof, of a cell surface protein, or is absent; TM is a transmembrane domain of a transmembrane protein; and ICD is an intracellular domain or a protein that facilitates the incorporation of the targeting moiety into the envelope of the viral particle, or is absent; wherein the targeting moiety having the formula of T-L1-Fc-L2-X1 has a formula of T- L1-Fc-L2-ECD-TM-ICD.
  • the stalk portion S1 comprises a formula of L3-X1, wherein L3 is a flexible peptide linker, and X1 is a polypeptide comprising a transmembrane domain; wherein the targeting moiety having the formula T-S1 has a formula of T-L3-X1.
  • the polypeptide comprising the transmembrane domain (X1) comprises a polypeptide having a formula of ECD-TM-ICD, wherein ECD is an extracellular domain, or a fragment thereof, of a cell surface protein, or is absent; TM is a transmembrane domain of a transmembrane protein; and ICD is an intracellular domain or a protein that -3- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT facilitates the incorporation of the targeting moiety into the envelope of the viral particle, or is absent; wherein the targeting moiety having the formula of T-L3-X1 has a formula of T-L3- ECD-TM-ICD.
  • the targeting moiety binds to CD7.
  • the targeting moiety comprises a polypeptide having a heavy chain variable region comprising a HCDR1 of SEQ ID NO: 30, a HCDR2 of SEQ ID NO: 31, and an HCDR3 of SEQ ID NO: 32, or variants of any of the forging.
  • the targeting moiety comprises a polypeptide having a light chain variable region comprising a LCDR1 of SEQ ID NO: 33, a LCDR2 of SEQ ID NO: 34, and an LCDR3 of SEQ ID NO: 35, or variants of any of the forging.
  • the heavy chain comprises a heavy chain variable region having at least 90% sequence identity to SEQ ID NO: 36.
  • the light chain comprises a light chain variable region having at least 90% sequence identity to SEQ ID NO: 37.
  • the targeting moiety that binds to CD7 comprises a polypeptide having a sequence having at least 90% sequence identity to SEQ ID NO: 38.
  • the targeting moiety that binds to CD7 comprises a polypeptide having a sequence having at least 90% sequence identity to SEQ ID NO: 39.
  • the targeting moiety binds to CD8.
  • the targeting moiety comprises a polypeptide having a heavy chain variable region comprising a HCDR1 of SEQ ID NO: 42, a HCDR2 of SEQ ID NO: 43, and an HCDR3 of SEQ ID NO: 44, or variants of any of the forging.
  • the targeting moiety comprises a polypeptide having a light chain variable region comprising a LCDR1 of SEQ ID NO: 45, a LCDR2 of SEQ ID NO: 46, and an LCDR3 of SEQ ID NO: 47, or variants of any of the forging.
  • the heavy chain comprises a heavy chain variable region having at least 90% sequence identity to SEQ ID NO: 48.
  • the light chain comprises a light chain variable region having at least 90% sequence identity to SEQ ID NO: 49.
  • the targeting moiety that binds to CD8 comprises a polypeptide having a sequence having at least 90% sequence identity to SEQ ID NO: 50.
  • the targeting moiety that binds to CD8 comprises a polypeptide having a sequence having at least 90% sequence identity to SEQ ID NO: 51.
  • the heterologous viral glycoprotein is a SVCV-G polypeptide as provided for herein. In some embodiments, the heterologous viral glycoprotein is a VSV-G polypeptide.
  • the VSV-G polypeptide comprises substitutions at positions I182, T214, and T352 of SEQ ID NO: 2.
  • the substitution at position 182 is I182D -4- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT or I182E.
  • the substitution at position 214 is T214N.
  • the substitution at position 352 is T352A.
  • the viral particle provided for herein further comprises a nucleic acid molecule encoding a heterologous molecule of interest.
  • the heterologous molecule of interest is as provided for herein.
  • the heterologous molecule of interest is a CAR.
  • the CAR comprises an antigen binding domain having a heavy chain variable region having at least 95% identity to SEQ ID NO: 89 and a light chain variable region having at least 95% identity to SEQ ID NO: 90. In some embodiments, the CAR comprises an antigen binding domain having a heavy chain variable region having at least 95% identity to SEQ ID NO: 94 and a light chain variable region having at least 95% identity to SEQ ID NO: 95. In some embodiments, the CAR comprises an antigen binding domain having an amino acid sequence having at least 95% identity to SEQ ID NO: 92. In some embodiments, the CAR comprises an antigen binding domain having an amino acid sequence having at least 95% identity to SEQ ID NO: 93.
  • the CAR comprises an antigen binding domain having an amino acid sequence having at least 95% identity to SEQ ID NO: 96. In some embodiments, CAR comprises an antigen binding domain having an amino acid sequence having at least 95% identity to SEQ ID NO: 97. In some embodiments, the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 99, at least 90% identity to SEQ ID NO: 99, at least 95% identity to SEQ ID NO: 99, at least 99% identity to SEQ ID NO: 99, or at least 100% identity to SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 105, at least 90% identity to SEQ ID NO: 105, at least 95% identity to SEQ ID NO: 105, at least 99% identity to SEQ ID NO: 105, or at least 100% identity to SEQ ID NO: 105. In some embodiments, the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 106, at least 90% identity to SEQ ID NO: 106, at least 95% identity to SEQ ID NO: 106, at least 99% identity to SEQ ID NO: 106, or at least 100% identity to SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 107, at least 90% identity to SEQ ID NO: 107, at least 95% identity to SEQ ID NO: 107, at least 99% identity to SEQ ID NO: 107, or at least 100% identity to SEQ ID NO: 107.
  • a method of infecting a cell is provided. In some embodiments the method comprises contacting the cell with a viral particle as provided for herein. In some embodiments, a method of infecting a cell in a subject is provided.
  • the method comprises administering to the subject a pharmaceutical composition comprising a viral particle as provided for herein.
  • a method of delivering a heterologous molecule of interest to a cell is provided.
  • the method comprises contacting the cell with a viral particle as provided for herein, wherein the viral particle comprises a nucleic acid molecule encoding the heterologous molecule of interest.
  • a method of delivering a heterologous molecule of interest to a cell in a subject is provided.
  • the method comprises administering to the subject a viral particle as provided for herein, wherein the viral particle comprises a nucleic acid molecule encoding the heterologous molecule of interest.
  • a method of treating a disease or disorder in a subject comprises administering to the subject a viral particle as provided for herein, wherein the viral particle comprises a nucleic acid molecule encoding a heterologous molecule of interest to treat the disease or disorder.
  • a method of treating an immune disorder is provided.
  • the method comprises administering to the subject a viral particle as provided for herein, wherein the viral particle comprises a nucleic acid molecule encoding a heterologous molecule of interest to treat the disease or disorder.
  • the immune disorder is multiple sclerosis (MS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), lupus nephritis (LN), warm autoimmune hemolytic anemia (WAHA), primary sclerosing cholangitis (PSC), or IgG4-related disease (IGG4-RD).
  • MS multiple sclerosis
  • SLE systemic lupus erythematosus
  • SSc systemic sclerosis
  • LN lupus nephritis
  • WAHA warm autoimmune hemolytic anemia
  • PSC primary sclerosing cholangitis
  • IgG4-RD IgG4-related disease
  • the viral particle comprises a heterologous viral glycoprotein and a targeting moiety comprising a polypeptide having the formula T-S1, wherein T is a target binding domain and S1 is a stalk portion.
  • the heterologous viral glycoprotein comprises a sequence selected from SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 52, or SEQ ID NO: 53.
  • the targeting binding domain comprises a -6- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT sequence selected from SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 50, or SEQ ID NO: 51.
  • the stalk portion S1 comprises a variant Fc protein comprising a sequence that is a variant of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28.
  • the variant of SEQ ID NO: 26 comprises one or more mutations selected from the group consisting of L234A, L235A, N297A, P329G, I253A, H310A, and H435A.
  • the variant of SEQ ID NO: 27 comprises one or more mutations selected from the group consisting of N297A, P329G, I253A, H310A, and H435A.
  • the variant of SEQ ID NO: 28 comprises one or more mutations selected from the group consisting of S228P, L235E, N297A, P329G, I253A, H310A and H435A.
  • the variant Fc protein further comprises a transmembrane domain comprising a sequence selected from SEQ ID NO: 61 or SEQ ID NO: 62.
  • a viral particle is provided.
  • the viral particle comprises a heterologous viral glycoprotein and a targeting moiety comprising a polypeptide having the formula T-S1, wherein T is a target binding domain and S1 is a stalk portion.
  • the heterologous viral glycoprotein comprises a sequence selected from SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 52, or SEQ ID NO: 53.
  • the target binding domain comprises a sequence selected from SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 50, or SEQ ID NO: 51.
  • the stalk portion S1 comprises a formula of L1-Fc-L2-X1, wherein L1 is a linker comprising a sequence selected from SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, or SEQ ID NO: 76, or is absent; Fc is a variant Fc protein comprising a sequence that is a variant of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28, L2 is a linker comprising a sequence selected from SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, or SEQ ID NO: 76, or is absent; and X1 is a polypeptide comprising a trans
  • the variant of SEQ ID NO: 26 comprises one or more mutations selected from the group consisting of L234A, L235A, N297A, P329G, I253A, H310A, and H435A.
  • the variant of SEQ ID NO: 27 comprises one or more mutations selected from the group consisting of N297A, P329G, I253A, H310A, and H435A.
  • the variant of SEQ ID NO: 28 comprises one or more mutations selected from the group consisting of S228P, L235E, N297A, P329G, I253A, H310A and H435A.
  • the polypeptide comprising a transmembrane domain has a formula of ECD-TM-ICD, wherein ECD is an extracellular domain having a sequence selected from SEQ ID NO: 59 or SEQ ID NO: 60, or -7- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT is a fragment thereof, or is absent; TM is a transmembrane domain having a sequence of SEQ ID NO: 61 or SEQ ID NO: 62 or a fragment thereof; and ICD is an intracellular domain or protein that facilitates the incorporation of the targeting moiety into the envelope of the viral particle, wherein the ICD comprises an env incorporation motif comprising an amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64, or the ICD is absent.
  • a viral particle comprises a heterologous viral glycoprotein and a targeting moiety comprising a polypeptide having the formula T-S1, wherein T is a target binding domain and S1 is a stalk portion.
  • the heterologous viral glycoprotein comprises a sequence selected from SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 52, or SEQ ID NO: 53.
  • the target binding domain comprises a sequence selected from SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 50, or SEQ ID NO: 51.
  • the stalk portion S1 comprises a formula of L1-Fc-L2-X1, wherein L1 is a linker comprising a sequence of SEQ ID NO: 55 or is absent; Fc is a variant Fc protein comprises a sequence that is a variant of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28, L2 is a linker comprising a sequence of SEQ ID NO: 55 or is absent; and X1 is a polypeptide comprising a transmembrane domain.
  • the variant of SEQ ID NO: 26 comprises one or more mutations selected from the group consisting of L234A, L235A, N297A, P329G, I253A, H310A, and H435A.
  • the variant of SEQ ID NO: 27 comprises one or more mutations selected from the group consisting of N297A, P329G, I253A, H310A, and H435A.
  • the variant of SEQ ID NO: 28 comprises one or more mutations selected from the group consisting of S228P, L235E, N297A, P329G, I253A, H310A and H435A.
  • the polypeptide comprising a transmembrane domain has a formula of ECD-TM-ICD, wherein ECD is an extracellular domain having a sequence of SEQ ID NO: 60, or a fragment thereof, or is absent; TM is a transmembrane domain having a sequence of SEQ ID NO: 62 or a fragment thereof; and ICD is an intracellular domain or protein that facilitates the incorporation of the targeting moiety into the envelope of the viral particle, wherein the ICD comprises an env incorporation motif comprising an amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64, or the ICD is absent.
  • a viral particle is provided.
  • the viral particle comprises a heterologous viral glycoprotein and a targeting moiety comprising a polypeptide having the formula T-S1, wherein T is a target binding domain and S1 is a stalk portion.
  • heterologous viral glycoprotein comprises a sequence selected from SEQ ID NO: 23 or SEQ ID NO: 25.
  • the target binding domain -8- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT comprises a of SEQ ID NO: 39.
  • the stalk portion S1 comprises a formula of L1-Fc-L2-X1, wherein L1 is a linker comprising a sequence of SEQ ID NO: 55; Fc is a variant Fc protein comprising a sequence of SEQ ID NO: 104, L2 is a linker and is absent; and X1 is a polypeptide comprising a transmembrane domain.
  • the polypeptide comprising a transmembrane domain has a formula of ECD-TM-ICD, wherein ECD is an extracellular domain having a sequence of SEQ ID NO: 60; TM is a transmembrane domain having a sequence of SEQ ID NO: 62; and ICD is an intracellular domain or protein that facilitates the incorporation of the targeting moiety into the envelope of the viral particle, wherein the ICD comprises an env incorporation motif comprising an amino acid sequence of SEQ ID NO: 63.
  • a viral particle is provided, wherein the viral particle comprises a heterologous viral glycoprotein and a targeting moiety.
  • the heterologous viral glycoprotein comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 23 or SEQ ID NO: 25, having at least 95% identity to SEQ ID NO: 23 or SEQ ID NO: 25, having at least 99% identity to SEQ ID NO: 23 or SEQ ID NO: 25, or having at least 100% identity to SEQ ID NO: 23 or SEQ ID NO: 25.
  • the targeting moiety comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 98, at least 95% identity to SEQ ID NO: 98, at least 99% identity to SEQ ID NO: 98, or at least 100% identity to SEQ ID NO: 98.
  • a viral particle comprising a heterologous viral glycoprotein and a targeting moiety.
  • the heterologous viral glycoprotein comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 52 or SEQ ID NO: 53, having at least 95% identity to SEQ ID NO: 52 or SEQ ID NO: 53, having at least 99% identity to SEQ ID NO: 52 or SEQ ID NO: 53, or having at least 100% identity to SEQ ID NO: 52 or SEQ ID NO: 53.
  • the targeting moiety comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 98, at least 95% identity to SEQ ID NO: 98, at least 99% identity to SEQ ID NO: 98, or at least 100% identity to SEQ ID NO: 98.
  • a viral particle is provided.
  • the viral particle comprises a heterologous viral glycoprotein and a targeting moiety comprising a polypeptide having the formula T-S1, wherein T is a target binding domain and S1 is a stalk portion.
  • the target binding domain comprises an amino acid sequence of SEQ ID NO: 38 or SEQ ID NO: 39.
  • the stalk portion S1 comprises a formula L3-X1, wherein L3 is a flexible peptide linker comprising an amino acid sequence of -9- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, or SEQ ID NO: 58 and X1 is a polypeptide linker comprising a transmembrane domain.
  • the polypeptide comprising a transmembrane domain has a formula of ECD-TM-ICD, wherein ECD is an extracellular domain comprising an amino acid sequence of SEQ ID NO: 59 or SEQ ID NO: 60, or is a fragment thereof, or is absent, TM is a transmembrane domain comprising an amino acid sequence of SEQ ID NO: 61 or SEQ ID NO: 62, and ICD is an intracellular domain or protein that facilitates the incorporation of the targeting moiety into the envelope of the viral particle, wherein the ICD comprises an env incorporation motif comprising an amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64, or the ICD is absent.
  • ECD is an extracellular domain comprising an amino acid sequence of SEQ ID NO: 59 or SEQ ID NO: 60, or is a fragment thereof, or is absent
  • TM is a transmembrane domain comprising an amino acid sequence of SEQ ID NO: 61 or SEQ ID NO: 62
  • ICD
  • a viral particle comprises a heterologous viral glycoprotein and a targeting moiety comprising a polypeptide having the formula T-S1, wherein T is a target binding domain and S1 is a stalk portion.
  • the target binding domain comprises an amino acid sequence of SEQ ID NO: 50 or SEQ ID NO: 51.
  • the stalk portion S1 comprises a formula L3-X1, wherein L3 is a flexible peptide linker comprising an amino acid sequence of SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, or SEQ ID NO: 58 and X1 is a polypeptide linker comprising a transmembrane domain.
  • the polypeptide comprising a transmembrane domain has a formula of ECD-TM-ICD, wherein ECD is an extracellular domain comprising an amino acid sequence of SEQ ID NO: 59 or SEQ ID NO: 60, or is a fragment thereof, or is absent, TM is a transmembrane domain comprising an amino acid sequence of SEQ ID NO: 61 or SEQ ID NO: 62, and ICD is an intracellular domain or protein that facilitates the incorporation of the targeting moiety into the envelope of the viral particle, wherein the ICD comprises an env incorporation motif comprising an amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64, or the ICD is absent.
  • ECD is an extracellular domain comprising an amino acid sequence of SEQ ID NO: 59 or SEQ ID NO: 60, or is a fragment thereof, or is absent
  • TM is a transmembrane domain comprising an amino acid sequence of SEQ ID NO: 61 or SEQ ID NO: 62
  • ICD
  • a viral particle comprises a heterologous viral glycoprotein and a targeting moiety comprising a polypeptide having the formula T-S1, wherein T is a target binding domain and S1 is a stalk portion.
  • the heterologous viral glycoprotein comprises a sequence of SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 52, or SEQ ID NO: 53.
  • the target binding domain comprises an amino acid sequence of SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 50, or SEQ ID NO: 51.
  • the stalk portion S1 comprises a formula L3-X1, wherein L3 is a flexible peptide linker comprising an amino acid sequence of SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, or SEQ ID NO: 58 and X1 is a polypeptide linker comprising a -10- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT transmembrane domain.
  • the polypeptide comprising a transmembrane domain has a formula of ECD-TM-ICD, wherein ECD is an extracellular domain comprising an amino acid sequence of SEQ ID NO: 59 or SEQ ID NO: 60, or is a fragment thereof, or is absent, TM is a transmembrane domain comprising an amino acid sequence of SEQ ID NO: 61 or SEQ ID NO: 62, and ICD is an intracellular domain or protein that facilitates the incorporation of the targeting moiety into the envelope of the viral particle, wherein the ICD comprises an env incorporation motif comprising an amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64, or the ICD is absent.
  • ECD is an extracellular domain comprising an amino acid sequence of SEQ ID NO: 59 or SEQ ID NO: 60, or is a fragment thereof, or is absent
  • TM is a transmembrane domain comprising an amino acid sequence of SEQ ID NO: 61 or SEQ ID NO: 62
  • ICD
  • a viral particle comprises a heterologous viral glycoprotein and a targeting moiety comprising a polypeptide having the formula T-S1, wherein T is a target binding domain and S1 is a stalk portion.
  • the heterologous viral glycoprotein comprises a sequence of SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 52, or SEQ ID NO: 53.
  • the target binding domain comprises an amino acid sequence of SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 50, or SEQ ID NO: 51.
  • the stalk portion S1 comprises a formula L3-X1, wherein L3 is a flexible peptide linker comprising an amino acid sequence of SEQ ID NO: 55, and X1 is a polypeptide linker comprising a transmembrane domain.
  • the polypeptide comprising a transmembrane domain has a formula of ECD-TM-ICD, wherein ECD is an extracellular domain comprising an amino acid sequence of SEQ ID NO: 59 or SEQ ID NO: 60, or is a fragment thereof, or is absent, TM is a transmembrane domain comprising an amino acid sequence of SEQ ID NO: 61 or SEQ ID NO: 62, and ICD is an intracellular domain or protein that facilitates the incorporation of the targeting moiety into the envelope of the viral particle, wherein the ICD comprises an env incorporation motif comprising an amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64, or the ICD is absent.
  • ECD is an extracellular domain comprising an amino acid sequence of SEQ ID NO: 59 or SEQ ID NO: 60, or is a fragment thereof, or is absent
  • TM is a transmembrane domain comprising an amino acid sequence of SEQ ID NO: 61 or SEQ ID NO: 62
  • ICD
  • a viral particle comprises a heterologous viral glycoprotein and a targeting moiety comprising a polypeptide having the formula T-S1, wherein T is a target binding domain and S1 is a stalk portion.
  • the heterologous viral glycoprotein comprises a sequence of SEQ ID NO: 23 or SEQ ID NO: 25.
  • the target binding domain comprises an amino acid sequence of SEQ ID NO: 39.
  • the stalk portion S1 comprises a formula L3-X1, wherein L3 is a flexible peptide linker comprising an amino acid sequence of SEQ ID NO: 55, and X1 is a polypeptide linker comprising a transmembrane domain.
  • the polypeptide comprising a transmembrane domain has -11- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT a formula of ECD-TM-ICD, wherein ECD is an extracellular domain comprising an amino acid sequence of SEQ ID NO: 59, TM is a transmembrane domain comprising an amino acid sequence of SEQ ID NO: 61, and ICD is an intracellular domain or protein that facilitates the incorporation of the targeting moiety into the envelope of the viral particle, wherein the ICD comprises an env incorporation motif comprising an amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64.
  • a viral particle is provided.
  • the viral particle comprises a heterologous viral glycoprotein and a targeting moiety comprising a polypeptide having the formula T-S1, wherein T is a target binding domain and S1 is a stalk portion.
  • the heterologous viral glycoprotein comprises a sequence of SEQ ID NO: 52 or SEQ ID NO: 53.
  • the target binding domain comprises an amino acid sequence of SEQ ID NO: 39.
  • the stalk portion S1 comprises a formula L3-X1, wherein L3 is a flexible peptide linker comprising an amino acid sequence of SEQ ID NO: 55, and X1 is a polypeptide linker comprising a transmembrane domain.
  • the polypeptide comprising a transmembrane domain has a formula of ECD-TM-ICD, wherein ECD is an extracellular domain comprising an amino acid sequence of SEQ ID NO: 59, TM is a transmembrane domain comprising an amino acid sequence of SEQ ID NO: 61, and ICD is an intracellular domain or protein that facilitates the incorporation of the targeting moiety into the envelope of the viral particle, wherein the ICD comprises an env incorporation motif comprising an amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64.
  • the viral particle as provided for herein further comprises a nucleic acid molecule encoding for a heterologous molecule of interest.
  • the heterologous molecule of interest is as provided for herein.
  • the heterologous molecule of interest is a CAR.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 99, at least 90% identity to SEQ ID NO: 99, at least 95% identity to SEQ ID NO: 99, at least 99% identity to SEQ ID NO: 99, or at least 100% identity to SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 105, at least 90% identity to SEQ ID NO: 105, at least 95% identity to SEQ ID NO: 105, at least 99% identity to SEQ ID NO: 105, or at least 100% identity to SEQ ID NO: 105. In some embodiments, the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 106, at least 90% identity to SEQ ID NO: 106, at least 95% identity to SEQ ID NO: 106, at least 99% identity to SEQ ID NO: 106, or at least 100% identity to SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 107, at least 90% identity to SEQ ID NO: 107, at least 95% identity to SEQ ID NO: 107, at least 99% identity to SEQ ID NO: 107, or at least 100% identity to SEQ ID NO: 107.
  • FIG. 1A and FIG. 1B illustrate crystal structures of VSV-G bound to LDL-R.
  • FIG. 1A illustrates the crystal structure of VSV-G bound to CR3 of the LDL-R.
  • FIG.1B illustrates the crystal structure of VSV-G bound to CR2 of the LDL-R.
  • FIG. 2A and FIG. 2B illustrate the effect of adding negatively charged amino acids to the VSV-G:LDL-R binding interface on native tropism and fusogenicity.
  • FIG.2A illustrates the titration of VSV-G constructs on SupT1 cells.
  • FIG. 2B illustrates functional titer of each construct calculated from the titration in FIG.2A.
  • FIG.3 illustrates an alignment of the ectodomains of different VSV-G proteins from different strains.
  • FIG.4 illustrates the effect of various VSV-G mutations on the serum stability of viral constructs in combination with a CD7 binder.
  • FIG.5 illustrates the effect of various VSV-G mutations on the serum stability of viral constructs in combination with a CD7 binder.
  • FIG. 6 illustrates the ability of various rhabdovirus G proteins to transduce SupT1 and PBMC cells alone or in combination with a CD7 binder.
  • FIG. 7A-L show flow cytometry data of human PBMCs transduced with exemplary vectors comprising CD7 binders as disclosed herein.
  • FIG. 7M shows flow cytometry data of human PBMCs transduced with exemplary vectors comprising CD7 binders as disclosed herein.
  • FIG. 8A-L shows flow cytometry data of non-human primate PBMCs transduced with exemplary vectors comprising CD7 binders as disclosed herein.
  • FIG.8M shows flow cytometry data of non-human primate PBMCs transduced with exemplary vectors comprising CD7 binders as disclosed herein.
  • FIG. 9A shows flow cytometry data of human PBMCs transduced with exemplary vectors comprising CD8 binders as disclosed herein.
  • FIG. 9B shows flow cytometry data of non-human primate PBMCs transduced with exemplary vectors comprising CD8 binders as disclosed herein.
  • FIG.10A illustrates the ability of VSV-G* pseudotyped lentiviral particles harboring a CD7 binder with a variant Fc stalk to transduce SupT1 cells as well as human and non-human primate PBMCs.
  • FIG 10B illustrates the transduction of cells in the absence of the CD7 binder.
  • FIG. 10C illustrates the transduction of human and non-human primate PBMCs in terms of MOI calculated from SupT1 titration.
  • VSV-G* denotes VSV-G (I182E, T214N, T352A).
  • FIG.11A illustrates the ability of VSV-G* pseudotyped lentiviral particles harboring a CD7 binder with a flexible stalk to transduce SupT1 cells as well as human and non-human primate PBMCs.
  • FIG. 11B illustrates the transduction of cells in the absence of the CD7 binder.
  • FIG 11C illustrates the transduction of human and non-human primate PBMCs in terms of MOI calculated from SupT1 titration.
  • VSV-G* denotes VSV-G (I182E, T214N, T352A).
  • FIG.12A illustrates the ability of viral particles harboring a CD7 binder with flexible stalks of varying length to transduce SupT1 cells in comparison to other IgG based binders.
  • FIG.12B illustrates the ability of viral particles harboring a CD7 binder with flexible stalks of varying length to transduce activated PBMC cells in comparison to other IgG based binders.
  • FIG.13A illustrates the ability of SVCV-G pseudotyped lentiviral particles harboring a CD7 binder with a variant Fc stalk to transduce SupT1 cells as well as human and non-human primate PBMCs.
  • FIG 13B illustrates the transduction of cells in the absence of the CD7 binder.
  • FIG. 13C illustrates the transduction of human and non-human primate PBMCs in terms of MOI calculated from SupT1 titration.
  • FIG.14A illustrates the ability of SVCV-G pseudotyped lentiviral particles harboring a CD7 binder with a flexible stalk to transduce SupT1 cells as well as human and non-human primate PBMCs.
  • FIG. 14B illustrates the transduction of cells in the absence of the CD7 binder.
  • FIG 14C illustrates the transduction of human and non-human primate PBMCs in terms of MOI calculated from SupT1 titration.
  • FIG.15A-D is a comparison of the ability of VSV-G* pseudotyped lentiviral particles (panels A and B) and SVCV-G pseudotyped lentiviral particles (panels C and D) to transduce SupT1 cells as well as human and non-human primate PBMCs.
  • VSV-G* denotes VSV-G (I182E, T214N, T352A).
  • FIG.16A-D is a comparison of the ability of VSV-G* pseudotyped lentiviral particles (panels A and B) and SVCV-G pseudotyped lentiviral particles (panels C and D) to transduce SupT1 cells as well as human and non-human primate PBMCs.
  • VSV-G* denotes VSV-G (I182E, T214N, T352A).
  • FIG. 17A-H illustrate the assessment of off target transduction by VSV-G* pseudotyped lentiviral particles harboring a CD7 binder with a variant Fc stalk delivering a -14- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT CD20 CAR (CAR20), CD19 CAR (SEQ ID NO: 107, SEQ ID NO: 105, or SEQ ID NO: 132), or control CAR.
  • FIG. 17A illustrates that the pseudotyped lentiviral particles were able to successfully transduce T cells (SupT1) with all CAR constructs.
  • FIG. 18A-B illustrate the ability of CAR19+ PBMCs transduced with a VSV-G* pseudotyped lentiviral particles delivering a CD19 CAR transgene as provided for herein to kill CD19+ B cells.
  • FIG. 18A illustrates the results for Daudi cells.
  • FIG. 18B illustrates the results for Raji cells.
  • FIG. 19A-C illustrate that B-cell killing induced by CAR19 expressing T-cells is CD19 dependent.
  • FIG. 19A illustrate the % B-cell killing of Raji-GFP cells, CD19 KO Raji cells, and CD20 KO Raji cells by PBMCs transduced with a CD19 CAR corresponding to SEQ ID NO: 105.
  • FIG. 19B illustrate the % B-cell killing of Raji-GFP cells, CD19 KO Raji cells, and CD20 KO Raji cells by PBMCs transduced with a CD19 CAR corresponding to SEQ ID NO: 107.
  • FIG.19C illustrate the % B-cell killing of Raji-GFP cells, CD19 KO Raji cells, and CD20 KO Raji cells by PBMCs transduced with a control CD20 targeted CAR.
  • FIG. 20A and B illustrate the results of an experiment to assess risk of generating CAR-resistant B cells.
  • FIG.20A illustrates the ability of CAR19 positive PBMCs to kill Rec- 1 cells either expressing the CAR19 or GFP.
  • FIG. 20B illustrates the results of CAR19 assessment of remaining cells.
  • FIG.21A illustrates the experimental design of a mouse model utilized herein.
  • FIG.21B illustrates the level of CAR19 (either SEQ ID NO: 105 or SEQ ID NO: 107) detectable in the blood of mice administered a VSV-G* pseudotyped lentiviral particles harboring a CD7 binder with a variant Fc stalk and the respective CAR19 transgene.
  • FIG. 22A and B illustrate B-cell depletion in mice administered a VSV-G* pseudotyped lentiviral particles harboring a CD7 binder with a variant Fc stalk and the respective CAR19 transgene.
  • FIG.22A illustrates B-cell depletion as measured by percentage of CD19 positive cells in the population of CD45 positive cells.
  • FIG.21B illustrates the level of CAR19 (either SEQ ID NO: 105 or SEQ ID NO: 107) detectable in the blood of mice administered a VSV-G* pseudotyped lentiviral particles harboring a CD7 binder with a
  • FIG. 22B illustrates B-cell -15- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT depletion as measured by percentage of CD20 positive cells in the population of CD45 positive cells.
  • FIG. 23A and B illustrate B-cell depletion in select organs of mice administered a VSV-G* pseudotyped lentiviral particles harboring a CD7 binder with a variant Fc stalk and the respective CAR19 transgene.
  • FIG.23A illustrates B-cell depletion in the spleen of mice as measured by CD19 and CD20 levels.
  • FIG.23B illustrates B-cell depletion in bone marrow as measured by CD19 and CD20 levels.
  • viral particles comprising a heterologous viral glycoprotein and a targeting moiety, wherein the targeting moiety comprises a polypeptide having the formula of T-S1, wherein T is a target binding domain, and S1 is a stalk portion.
  • S1 comprises a mutant Fc polypeptide that can be, for example, linked to a transmembrane domain as provided for herein.
  • S1 comprises flexible polypeptides as provided for herein. The mutant Fc polypeptides or the flexible polypeptides can be incorporated into a viral particle to help facilitate the targeting of the viral particle to a specific cell type.
  • the viral particle can comprise VSV-G proteins that can be used, for example, to pseudotype a virus, such as a lentivirus.
  • the pseudotyped viral-like particles are pseudotyped using viral glycoproteins of a vesicular stomatitis New Jersey virus strain, a vesicular stomatitis Indiana virus strain, a vesicular stomatitis Alagoas virus strain, a vesicular stomatitis Maraba virus strain, or a vesicular stomatitis Carajas virus strain. Examples of such proteins are provided for herein.
  • the terms “a” or “an” means that “at least one” or “one or more” unless the context clearly indicates otherwise.
  • the term “about” means that the numerical value is approximate and small variations would not significantly affect the practice of the disclosed embodiments. Where a numerical limitation is used, unless indicated otherwise by the context, “about” means the numerical value can vary by ⁇ 10% and remain within the scope of the disclosed embodiments. Additionally, where a phrase recites “about x to y,” the term “about” modifies both x and y and can be used interchangeably with the phrase “about x to about y” unless context dictates differently.
  • the term “individual” or “subject,” or “patient” used interchangeably, means any animal, including mammals, such as mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, or primates, such as humans.
  • the terms “comprising” (and any form of comprising, such as “comprise”, “comprises”, and “comprised”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”), or “containing” (and any form of containing, such as “contains” and “contain”), are inclusive or open-ended and do not exclude additional, unrecited elements or method steps.
  • any step or composition that uses the transitional phrase of “comprise” or “comprising” can also be said to describe the same with the transitional phase of “consisting of” or “consists.”
  • the term “contacting” means bringing together of two elements in an in vitro system or an in vivo system.
  • “contacting” virus or vector described herein with an individual or patient or cell includes the administration of the virus to an individual or patient, such as a human, as well as, for example, introducing a compound into a sample containing a cellular or purified preparation containing the cell.
  • the term “fused” or “linked” when used in reference to a protein having different domains or heterologous sequences means that the protein domains are part of the same peptide chain that are connected to one another with either peptide bonds or other covalent bonding.
  • the domains or section can be linked or fused directly to one another or another domain or peptide sequence can be between the two domains or sequences and such sequences would still be considered to be fused or linked to one another.
  • the various domains or proteins provided for herein are linked or fused directly to one another or a linker sequences, such as the glycine/serine sequences described herein link the two domains together.
  • a “disease” is a state of health of an animal wherein the animal cannot maintain homeostasis, and wherein if the disease is not ameliorated then the animal’s health continues to deteriorate.
  • a “disorder” in an animal is a state of health in which the animal is able to maintain homeostasis, but in which the animal’s state of health is less favorable than it would be in the absence of the disorder. Left untreated, a disorder does not necessarily cause a further decrease in the animal’s state of health.
  • Effective amount or “therapeutically effective amount” are used interchangeably herein, and refer to an amount of a compound, formulation, material, or composition, as described herein effective to achieve a particular biological result or provides a therapeutic or prophylactic benefit. Such results may include, but are not limited to an amount that when administered to a mammal, causes a detectable level of immune cell activation compared to the immune cell activation detected in the absence of the composition. The immune response can be readily assessed by a plethora of art-recognized methods.
  • Encoding refers to the inherent property of specific sequences of nucleotides in a polynucleotide, such as a gene, a cDNA, or an mRNA, to serve as templates for synthesis of other polymers and macromolecules in biological processes having either a defined sequence of nucleotides (i.e., rRNA, tRNA and mRNA) or a defined sequence of amino acids and the biological properties resulting therefrom.
  • a gene encodes a protein if transcription and translation of mRNA corresponding to that gene produces the protein in a cell or other biological system.
  • Both the coding strand, the nucleotide sequence of which is identical to the mRNA sequence and is usually provided in sequence listings, and the non-coding strand, used as the template for transcription of a gene or cDNA, can be referred to as encoding the protein or other product of that gene or cDNA.
  • “Expression vector” refers to a vector comprising a recombinant polynucleotide comprising expression control sequences operatively linked to a nucleotide sequence to be expressed.
  • An expression vector comprises sufficient cis-acting elements for expression; other elements for expression can be supplied by the host cell or in an in vitro expression system.
  • Expression vectors include all those known in the art, such as cosmids, plasmids (e.g., naked or contained in liposomes) and viruses (e.g., Sendai viruses, lentiviruses, retroviruses, adenoviruses, and adeno-associated viruses) that incorporate the recombinant polynucleotide.
  • ex vivo in reference to a cell being transduced, transfected or transformed ex vivo, refers to a cell being transduced, transfected or transformed outside of the subject, that is with the cells being removed from the subject before such cells are transduced, transfected or transformed.
  • Identity refers to the subunit sequence identity between two polymeric molecules such as between two nucleic acid or amino acid molecules, such as, between two polynucleotide or polypeptide molecules.
  • two amino acid sequences When two amino acid sequences have the same residues at the same positions; e.g., if a position in each of two polypeptide molecules is occupied by an Arginine, then they are identical at that position.
  • the identity or extent to which two amino acid or two nucleic acid sequences have the same residues at the same positions in an alignment is often expressed as a percentage.
  • the identity between two amino acid or two nucleic acid sequences is a direct function of the number of matching or identical positions; e.g., if half of the positions in two sequences are identical, the two sequences are 50% identical; if 90% of the positions (e.g., 9 of 10), are matched or identical, the two amino acids sequences are 90% identical.
  • substantially identical is meant a polypeptide or nucleic acid molecule exhibiting at least 50% identity to a reference amino acid sequence (for example, any one of the amino acid sequences described herein) or nucleic acid sequence (for example, any one of the nucleic acid sequences described herein). In some embodiments, such a sequence is at least 60%, 80% or 85%, or 90%, 95% or even 99% identical at the amino acid level or nucleic acid to the sequence used for comparison. Other percentages of identity in reference to specific sequences are described herein.
  • Sequence identity can be measured/determined using sequence analysis software (for example, Sequence Analysis Software Package of the Genetics Computer Group, University of Wisconsin Biotechnology Center, 1710 University Avenue, Madison, Wis.53705, BLAST, BESTFIT, GAP, or PILEUP/PRETTYBOX programs). Such software matches identical or similar sequences by assigning degrees of homology to various substitutions, deletions, and/or other modifications. Conservative substitutions typically include substitutions within the following groups: glycine, alanine; valine, isoleucine, leucine; aspartic acid, glutamic acid, asparagine, glutamine; serine, threonine; lysine, arginine; and phenylalanine, tyrosine.
  • a BLAST program may be used, with a probability score between e3 and e100 indicating a closely related sequence.
  • sequence identity is determined by using BLAST with the default settings.
  • -19- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT To the extent embodiments provided for herein, includes composition comprising various proteins, these proteins may, in some instances, comprise amino acid sequences that have sequence identity to the amino acid sequences disclosed herein. Therefore, in certain embodiments, depending on the particular sequence, the degree of sequence identity is preferably greater than 50% (e.g.
  • amino acids are generally divided into four families: (1) acidic i.e. aspartate, glutamate; (2) basic i.e. lysine, arginine, histidine; (3) non polar i.e. alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan; and (4) uncharged polar i.e. glycine, asparagine, glutamine, cysteine, serine, threonine, tyrosine. Phenylalanine, tryptophan, and tyrosine are sometimes classified jointly as aromatic amino acids.
  • the proteins may have one or more (e.g.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) single amino acid deletions relative to the disclosed protein sequences.
  • the proteins may also include one or more (e.g.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) insertions (e.g. each of 1, 2, 3, 4 or 5 amino acids) relative to the disclosed protein sequences.
  • the phrase “in vivo” in reference to a cell being transduced, transfected or transformed in vivo refers to a cell being transduced, transfected or transformed in the subject without the cells being removed from the subject before such cells are transduced, transfected or transformed.
  • isolated means altered or removed from the natural state.
  • a nucleic acid or a peptide naturally present in a living animal is not “isolated,” but the same nucleic acid or peptide partially or completely separated from the coexisting materials of its natural state is “isolated.”
  • An isolated nucleic acid or protein can exist in substantially purified form, or can exist in a non-native environment such as, for example, a host cell.
  • a “lentivirus” as used herein refers to a genus of the Retroviridae family that is able to infect non-dividing cells. Non-limiting examples of lentiviruses are HIV, SIV, and FIV.
  • Vectors or viral-like particles derived from lentiviruses can be used to transduce cells and deliver genes or other molecules and have them expressed in a cell either in vitro (ex-vivo) or in vivo.
  • modified as used herein, is meant a changed state or structure of a molecule or cell as provided herein.
  • Molecules may be modified in many ways, including chemically, structurally, and functionally, such as mutations, substitutions, insertions, or deletions (e.g. internal deletions truncations). Cells may be modified through the introduction of nucleic acids or the expression of heterologous proteins.
  • a “nucleotide sequence encoding an amino acid sequence” includes all nucleotide sequences that are degenerate versions of each other and that encode the same amino acid sequence.
  • nucleotide sequence is represented by a DNA sequence (i.e., A, T, C, G)
  • this also provides the corresponding RNA sequence (i.e., A, U, C, G) in which “U” replaces “T.”
  • parenteral administration of a composition includes, e.g., subcutaneous (s.c.), intravenous (i.v.), intramuscular (i.m.), or intrasternal injection, or infusion techniques.
  • polynucleotide as used herein is defined as a chain of nucleotides.
  • nucleic acids are polymers of nucleotides.
  • nucleic acids and “polynucleotides” as used herein are interchangeable.
  • polynucleotides include, but are not limited to, all nucleic acid sequences which are obtained by any methods available in the art, including, without limitation, recombinant methods, i.e., the cloning of nucleic acid sequences from a recombinant library or a cell genome, using cloning technology and PCR, and the like, and by synthetic means.
  • peptide As used herein, the terms “peptide,” “polypeptide,” and “protein” are used interchangeably, and refer to a compound comprised of a plurality of amino acid residues -21- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT covalently linked by peptide bonds.
  • the term refers to both short chains, which also commonly are referred to in the art as peptides, oligopeptides and oligomers, for example, and to longer chains, which generally are referred to in the art as proteins, of which there are many types.
  • Polypeptides include, for example, biologically active fragments, substantially homologous polypeptides, oligopeptides, homodimers, heterodimers, variants of polypeptides, modified polypeptides, derivatives, analogs, fusion proteins, among others.
  • the polypeptides include natural peptides, recombinant peptides, synthetic peptides, or a combination thereof.
  • heterologous viral structural protein and “heterologous viral glycoprotein” as used herein are used synonymously and interchangeably.
  • heterologous viral structural protein is understood to be referring to a “heterologous viral glycoprotein” and vice versa.
  • the host range of the vector particles can thus be expanded or altered depending on the type of cell surface receptor used by the glycoprotein.
  • a virus can be pseudotyped with a VSV-G mutant protein as provided for herein.
  • an antibody which recognizes a specific antigen, but does not substantially recognize or bind other molecules in a sample.
  • an antibody that specifically binds to an antigen from one species may also bind to that antigen from one or more species. But, such cross- species reactivity does not itself alter the classification of an antibody as specific.
  • an antibody that specifically binds to an antigen may also bind to different allelic forms of the antigen. However, such cross reactivity does not itself alter the classification of an antibody as specific.
  • the terms “specific binding” or “specifically binding,” can be used in reference to the interaction of an antibody, a protein, or a peptide with a second chemical species, to mean that the interaction is dependent upon the presence of a particular structure (e.g., an antigenic determinant or epitope) on the chemical species; for example, an antibody recognizes and binds to a specific protein structure rather than to proteins generally. If an antibody is specific for epitope “A”, the presence of a molecule containing epitope A (or free, unlabeled A), in a reaction containing labeled “A” and the antibody, will reduce the amount of labeled A bound to the antibody.
  • a particular structure e.g., an antigenic determinant or epitope
  • the targeting moieties described herein that can be used to target the viral particles comprising the mutant -22- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT VSV-G protein, or other viral structural proteins used to pseudotype a virus can specifically bind to their target.
  • the term “subject” includes living organisms, including those in which an immune response can be elicited (e.g., mammals).
  • a “subject” or “patient,” as used therein, may be a human or non-human mammal.
  • Non-human mammals include, for example, livestock and pets, such as ovine, bovine, porcine, canine, non-human primates, feline and murine mammals.
  • the subject is human.
  • the term “therapeutic” as used herein means a treatment and/or prophylaxis. A therapeutic effect is obtained by suppression, remission, or eradication of a disease state.
  • the term “transfected” or “transformed” or “transduced” as used herein refers to a process by which exogenous nucleic acid is transferred or introduced into a cell.
  • a “transfected” or “transformed” or “transduced” cell is one which has been transfected, transformed or transduced with exogenous nucleic acid.
  • the cell includes the primary subject cell and its progeny. In some embodiments, the transfection, transformation, or transduction is performed or occurs in vivo.
  • a “vector” is a composition of matter which comprises an isolated nucleic acid encoding a protein or a peptide.
  • vectors are known in the art including, but not limited to, linear polynucleotides, plasmids, DNA, and RNA.
  • viral vectors include, but are not limited to, Sendai viral vectors, adenoviral vectors, adeno-associated virus vectors, retroviral vectors, lentiviral vectors, and the like.
  • a “carrier” or “delivery vehicle” includes viral particles, viruses, polylysine compounds, and liposomes, which facilitate transfer of nucleic acid into cells.
  • a carrier or delivery vehicle can also be used to deliver a protein or peptide to a cell.
  • a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, and 6.
  • DOCKET NO: INH-029WO PATENT This applies regardless of the breadth of the range.
  • a range that is disclosed also includes the endpoints of the range.
  • Viral Particles Comprising Heterologous Viral Glycoprotein and Targeting Moiety
  • viral particles are provided comprising a heterologous viral glycoprotein and a targeting moiety.
  • the targeting moiety comprises a polypeptide having the formula T-S1, wherein T is a target binding domain, and S1 is a stalk portion.
  • S1 comprises a variant Fc protein, wherein the variant Fc protein comprises a transmembrane domain, such as, but not limited to a CD8 or CD28 transmembrane domain.
  • the stalk portion S 1 comprises an N-terminus to C-terminus orientation of variant Fc – transmembrane domain.
  • the variant Fc protein comprises an effector mutation, wherein the effector mutation inhibits the interaction between the Fc protein and a Fc interacting protein, such as Fc ⁇ R, C1q, FcR ⁇ , or FcRn.
  • the S1 stalk portion is attached to the surface of the viral particle through the transmembrane domain.
  • the variant Fc protein is a variant of an IgG1 Fc, IgG2 Fc or IgG4 Fc protein.
  • the variant Fc protein comprises a variant of a sequence of SEQ ID NO: 26 (IgG1 Fc), SEQ ID NO: 27 (IgG2 Fc), or SEQ ID NO: 28 (IgG4 Fc).
  • the variant Fc protein is a variant IgG1 Fc protein (SEQ ID NO: 26).
  • the variant IgG1 Fc protein comprises one or more of the mutations that corresponds to those selected from the group consisting of: L234A, L235A, N297A, P329G, I253A, H310A, and H435A of SEQ ID NO: 26, numbered according to the EU numbering index of Kabat as described in Edelman, G M et al. “The covalent structure of an entire gammaG immunoglobulin molecule.” Proceedings of the National Academy of Sciences of the United States of America vol. 63,1 (1969): 78-85.
  • the variant IgG1 Fc protein comprises a mutation that corresponds to L234A and L235A of SEQ ID NO: 26. In some embodiments, the variant IgG1 Fc protein comprises a mutation that corresponds to N297A of SEQ ID NO: 26. In some embodiments, the variant IgG1 Fc protein comprises a mutation that corresponds to P329G of SEQ ID NO: 26.
  • the variant -24- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT IgG1 Fc protein comprises a mutation that corresponds to L234A, L235A, N297A, and P329G of SEQ ID N: 26.
  • the variant IgG1 Fc protein comprises a mutation that corresponds to I253A of SEQ ID NO: 26.
  • the variant IgG1 Fc protein comprises a mutation that corresponds to H310A of SEQ ID NO: 26.
  • the variant IgG1 Fc protein comprises a mutation that corresponds to H435A of SEQ ID NO: 26.
  • the variant IgG1 Fc protein comprises a mutation that corresponds to I253A, H310A, and H435A of SEQ ID NO: 26. In some embodiments, the variant IgG1 Fc protein comprises a mutation that corresponds to L234A, L235A, N297A, P329G, I253A, H310A, and H435A of SEQ ID NO: 26. In some embodiments, the variant Fc protein comprising a variant IgG1 Fc protein comprises a truncation of the IgG1 Fc sequence. The truncation can comprise the deletion of any number of amino acids from the N-terminus, the C-terminus, or both of the IgG1 Fc sequence.
  • the variant Fc protein comprising a variant IgG1 Fc protein comprises a truncation of SEQ ID NO: 26.
  • the truncation can comprises the deletion of any number of amino acids from the N-terminus, the C-terminus, or both of SEQ ID NO: 26.
  • the truncation comprises the deletion of amino acids from the N-terminus of SEQ ID NO: 26.
  • the truncation comprises the deletion of amino acids from the C-terminus of SEQ ID NO: 26.
  • the truncation comprises the deletion of amino acids from both the N-terminus and the C-terminus of SEQ ID NO: 26.
  • the truncation of SEQ ID NO: 26 comprises an amino acid sequence of SEQ ID NO: 103: EPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS HEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF SCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 103)
  • the variant IgG1 Fc protein comprises one or more mutations relative to SEQ ID NO: 103 selected from the group consisting of: L19A, L20A, N82A, P114G, I38A, H95A, and H220A.
  • positions L19, L20, N82, P114, I38, H95, and H220 are in reference to SEQ ID NO: 103 only.
  • positions L234, L235, N297, P329, I253, H310, and H435 numbered according to the EU numbering system of Kabat correspond to positions L19, L20, N82, P114, I38, H95, and H220, respectively, of SEQ ID NO: 103.
  • Any of the mutations L19A, L20A, N82A, P114G, I38A, H95A, and H220A of SEQ ID NO: 103 may be present of absent and the mutations may be combined in any combination.
  • the variant IgG1 Fc -25- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT protein comprises a mutation that corresponds to L19A and L20A of SEQ ID NO: 103. In some embodiments, the variant IgG1 Fc protein comprises a mutation that corresponds to N82A of SEQ ID NO: 103. In some embodiments, the variant IgG1 Fc comprises a mutation that corresponds to P114G of SEQ ID NO: 103. In some embodiments, the variant IgG1 Fc comprises a mutation that corresponds to L19A, L20A, N82A, and P114G of SEQ ID NO: 103.
  • the variant IgG1 Fc protein comprises a mutation that corresponds to I38A of SEQ ID NO: 103. In some embodiments, the variant IgG1 Fc protein comprises a mutation that corresponds to H95A of SEQ ID NO: 103. In some embodiments, the variant IgG1 Fc protein comprises a mutation that corresponds to H220A of SEQ ID NO: 103. In some embodiments, the variant IgG1 Fc protein comprises a mutation that corresponds to I38A, H95A, and H220A of SEQ ID NO: 103.
  • the variant IgG1 Fc protein comprises a mutation that corresponds to L19A, L20A N82A, P114G, I38A, H95A, and H220A of SEQ ID NO: 103. In some embodiments, the variant IgG1 Fc protein comprises a mutation that corresponds to each of L18A, L19A N82A, P114G, I38A, H95A, and H220A of SEQ ID NO: 103.
  • variant IgG1 protein that comprises each of L18A, L19A N82A, P114G, I38A, H95A, and H220A is shown below in the amino acid sequence of SEQ ID NO: 104: EPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMASRTPEVTCVVVDVS HEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLAQDWLNGKEY KCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF SCSVMHEALHNAYTQKSLSPGK (SEQ ID NO: 104)
  • the variant Fc protein is a variant IgG2 Fc protein (SEQ ID NO: 27).
  • the variant IgG2 Fc protein comprises one or more mutations selected from the group consisting of: N297A, P329G, I253A, H310A, and H435A as those position correspond to SEQ ID NO: 27, numbered according to the EU numbering index of Kabat. Any of the mutations N297A, P329G, I253A, H310A, and H435A of SEQ ID NO: 27 may be present or absent and the mutations may be combined in any combination. In some embodiments, the variant IgG2 Fc protein comprises a mutation that corresponds to N297A of SEQ ID NO: 27.
  • the variant IgG2 Fc protein comprises a mutation that corresponds to P329G of SEQ ID NO: 27. In some embodiments, the variant IgG2 Fc protein comprises a mutation that corresponds to N297A and P329G of SEQ ID NO: 27. In some embodiments, the variant IgG2 Fc protein comprises a mutation that corresponds to I253A of SEQ ID NO: 27. In some embodiments, the variant IgG2 Fc protein comprises a mutation that -26- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT corresponds to H310A of SEQ ID NO: 27.
  • the variant IgG2 Fc protein comprises a mutation that corresponds to H435A of SEQ ID NO: 27. In some embodiments, the variant IgG2 Fc protein comprises a mutation that corresponds to I253A, H310A, and H435A of SEQ ID NO: 27. In some embodiments, the variant Fc protein comprising a variant IgG2 Fc protein comprises a truncation of the IgG2 Fc sequence. The truncation can comprise the deletion of any number of amino acids from the N-terminus, the C-terminus, or both of the IgG2 Fc sequence.
  • the variant Fc protein comprising a variant IgG2 Fc protein comprises a truncation of SEQ ID NO: 27.
  • the truncation can comprises the deletion of any number of amino acids from the N-terminus, the C-terminus, or both of SEQ ID NO: 27.
  • the truncation comprises the deletion of amino acids from the N-terminus of SEQ ID NO: 27.
  • the truncation comprises the deletion of amino acids from the C-terminus of SEQ ID NO: 27.
  • the truncation comprises the deletion of amino acids from both the N-terminus and the C-terminus of SEQ ID NO: 27.
  • the variant Fc protein is a variant IgG4 Fc protein (SEQ ID NO: 28).
  • the variant IgG4 Fc protein comprises one or more mutations selected from the group consisting of: S228P, L235E, N297A, P329G, I253A, H310A, and H435A as those positions correspond to SEQ ID NO: 28, numbered according to the EU numbering index of Kabat. Any of the mutations S228P, L235E, N297A, P329G, I253A, H310A, and H435A of SEQ ID NO: 28 may be present or absent and the mutations may be combined in any combination.
  • the variant IgG4 Fc protein comprises a mutation that corresponds to S228P of SEQ ID NO: 28. In some embodiments, the variant IgG4 Fc protein comprises a mutation that corresponds to L235E of SEQ ID NO: 28. In some embodiments, the variant IgG4 Fc protein comprises a mutation that corresponds to N297A of SEQ ID NO: 28. In some embodiments, the variant IgG4 Fc protein comprises a mutation that corresponds to P329G of SEQ ID NO: 28. In some embodiments, the variant IgG4 Fc protein comprises a mutation that corresponds to S228P, L235E, N297A, and P329G of SEQ ID NO: 28.
  • the variant IgG4 Fc protein comprises a mutation that corresponds to I253A of SEQ ID NO: 28. In some embodiments, the variant IgG4 Fc protein comprises a mutation that corresponds to H310A of SEQ ID NO: 28. In some embodiments, the variant IgG4 Fc protein comprises a mutation that corresponds to H435A of SEQ ID NO: 28. In some embodiments, the variant IgG4 Fc protein comprises a mutation that corresponds to I253A, H310A, and H435A of SEQ ID NO: 28.
  • the variant Fc protein comprising a variant IgG4 Fc protein comprises a truncation of the IgG4 Fc sequence.
  • the truncation can comprise the deletion of any number of amino acids from the N-terminus, the C-terminus, or both of the IgG4 Fc sequence.
  • the variant Fc protein comprising a variant IgG4 Fc protein comprises a truncation of SEQ ID NO: 28.
  • the truncation can comprises the deletion of any number of amino acids from the N-terminus, the C-terminus, or both of SEQ ID NO: 28.
  • the truncation comprises the deletion of amino acids from the N-terminus of SEQ ID NO: 28. In some embodiments, the truncation comprises the deletion of amino acids from the C-terminus of SEQ ID NO: 28. In some embodiments, the truncation comprises the deletion of amino acids from both the N-terminus and the C-terminus of SEQ ID NO: 28.
  • the stalk portion S1 comprising a variant Fc protein is given by the formula L1-Fc-L2-X1, wherein L1 is a linker or absent; Fc is the variant Fc protein; L2 is a linker or absent; and X1 is a polypeptide comprising the transmembrane domain.
  • the targeting moiety comprising the formula T-S1 may also be given by the formula T-L1-Fc-L2-X1, wherein: T is a target binding domain; L1 is a linker or absent; Fc is the variant Fc protein; L2 is a linker or absent; and X1 is a polypeptide comprising the transmembrane domain. Therefore, it is to be understood that, in some embodiments, the stalk portion S1 may be given by the formula L1-Fc-L2- X1.
  • the target binding domain T is as provided for herein.
  • the variant Fc protein is as provided for herein.
  • L1 and L2 are each, independently, a polypeptide linker.
  • the polypeptide linker comprises (GGGGA)n (SEQ ID NO: 54), (GGGGS)n (SEQ ID NO: 55), (EAAAK)n (SEQ ID NO: 73), A(EAAAK)nA (SEQ ID NO: 74), (XP)n (SEQ ID NO: 75), wherein X is Ala, Lys, or Glu, GSAGSAAGSGEF (SEQ ID NO: 56), KESGSVSSEQLAQFRSLD (SEQ ID NO: 57), EGKSSGSGSESKST (SEQ ID NO: 58), AEAAAKEAAAKA (SEQ ID NO: 76), or a combination thereof, wherein each n is, independently, 1-5.
  • each n is, independently, 1. In some embodiments, each n is, independently, 2. In some embodiments, each n is, independently, 3. In some embodiments, each n is, independently, 4. In some embodiments, each n is, independently, 5. In some embodiments, each n is, independently, greater than 5. In some embodiments, L1 is absent. In some embodiments, L1 is (GGGGA)n (SEQ ID NO: 54) or (GGGGS)n (SEQ ID NO: 55), wherein each n is, independently, 1-5. In some embodiments, L1 is (GGGGA)n (SEQ ID NO: 54) or (GGGGS)n (SEQ ID NO: 55), wherein each n is, independently, 1.
  • L1 is (GGGGA)n (SEQ ID NO: 54) or (GGGGS)n (SEQ ID NO: 55), wherein -28- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT each n is, independently, 2.
  • L1 is (GGGGA)n (SEQ ID NO: 54) or (GGGGS)n (SEQ ID NO: 55), wherein each n is, independently, 3.
  • L1 is (GGGGA)n (SEQ ID NO: 54) or (GGGGS)n (SEQ ID NO: 55), wherein each n is, independently, 4.
  • L1 is (GGGGA)n (SEQ ID NO: 54) or (GGGGS)n (SEQ ID NO: 55), wherein each n is, independently, 5.
  • L1 is (GGGGA)n (SEQ ID NO: 54) or (GGGGS)n (SEQ ID NO: 55), wherein each n is, independently, greater than 5.
  • L2 is absent.
  • L2 is (GGGGA)n (SEQ ID NO: 54) or (GGGGS)n (SEQ ID NO: 55), wherein each n is, independently, 1-5.
  • L2 is (GGGGA)n (SEQ ID NO: 54) or (GGGGS)n (SEQ ID NO: 55), wherein each n is, independently, 1.
  • L 2 is (GGGGA) n (SEQ ID NO: 54) or (GGGGS)n (SEQ ID NO: 55), wherein each n is, independently, 2.
  • L2 is (GGGGA)n (SEQ ID NO: 54) or (GGGGS)n (SEQ ID NO: 55), wherein each n is, independently, 3.
  • L2 is (GGGGA)n (SEQ ID NO: 54) or (GGGGS)n (SEQ ID NO: 55), wherein each n is, independently, 4.
  • L2 is (GGGGA)n (SEQ ID NO: 54) or (GGGGS)n (SEQ ID NO: 55), wherein each n is, independently, 5. In some embodiments, L2 is (GGGGA)n (SEQ ID NO: 54) or (GGGGS)n (SEQ ID NO: 55), wherein each n is, independently, greater than 5.
  • X1 comprises a polypeptide having a formula of ECD-TM- ICD, wherein ECD is an extracellular domain, or a fragment thereof, of a cell surface protein, or is absent; TM is a transmembrane domain of a transmembrane protein; and ICD is an intracellular domain of a protein or a protein that facilitates the incorporation of the targeting moiety into the envelope of the viral particle, or is absent.
  • the targeting moiety comprising the formula T-S1 that may also be given by the formula T-L1- Fc-L2-X1 may also be given by the formula T-L1-Fc-L2-ECD-TM-ICD, wherein T is a target binding domain; L1 is a linker or absent; Fc is the variant Fc protein; L2 is a linker or absent; ECD is an extracellular domain, or a fragment thereof, of a cell surface protein, or is absent; TM is a transmembrane domain of a transmembrane protein; and ICD is an intracellular domain of a protein or a protein that facilitates the incorporation of the targeting moiety into the envelope of the viral particle, or is absent.
  • the stalk portion S1 may be given by the formula L1-Fc-L2- ECD-TM-ICD. In some embodiments, the stalk portion S1 does not comprise a variant Fc region. In some embodiments, the stalk portion S1 is given by the formula L3-X1, wherein L3 is a flexible peptide linker and X1 is a polypeptide comprising a transmembrane domain as provided for herein.
  • the targeting moiety comprising the formula T-S1 -29- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT may also be given by the formula T-L3-X1, wherein T is a target binding domain, L3 is a flexible peptide linker, and X1 is a polypeptide comprising a transmembrane domain as provided for herein. Therefore, it is to be understood that, in some embodiments, the stalk portion S1 may be given by the formula L3-X1. In some embodiments, the S1 stalk portion is attached to the surface of the viral particle through the transmembrane domain.
  • the flexible peptide linker L3 may be any flexible peptide linker.
  • L3 is selected from the group of flexible linkers including, but not limited to, (GGGGA)n (SEQ ID NO: 54), (GGGGS)n (SEQ ID NO: 55), GSAGSAAGSGEF (SEQ ID NO: 56), KESGSVSSEQLAQFRSLD (SEQ ID NO: 57), EGKSSGSGSESKST (SEQ ID NO: 58), or any combination thereof, wherein each n is, independently, an integer selected from 1-4. In some embodiments, each n is, independently, an integer selected from 1-4, 1-5, 1-6, 1-7, 1-8, 1-9, or 1-10. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3.
  • n is 4. In some embodiments, n is 5. In some embodiments, n is 6. In some embodiments, n is 7. In some embodiments, n is 8. In some embodiments, n is 9. In some embodiments, n is 10. In some embodiments, each n is, independently, greater than 10. In some embodiments, L3 is (GGGGA)n (SEQ ID NO: 54) and n is 1. In some embodiments, L3 is (GGGGA)n (SEQ ID NO: 54) and n is 2. In some embodiments, L3 is (GGGGA)n (SEQ ID NO: 54) and n is 3. In some embodiments, L3 is (GGGGA)n (SEQ ID NO: 54) and n is 4.
  • L3 is (GGGGA)n (SEQ ID NO: 54) and n is 5. In some embodiments, L3 is (GGGGA)n (SEQ ID NO: 54) and n is 6. In some embodiments, L3 is (GGGGA)n (SEQ ID NO: 54) and n is 7. In some embodiments, L3 is (GGGGA)n (SEQ ID NO: 54) and n is 8. In some embodiments, L3 is (GGGGA)n (SEQ ID NO: 54) and n is 9. In some embodiments, L3 is (GGGGA)n (SEQ ID NO: 54) and n is 10. In some embodiments, L3 is (GGGGA)n (SEQ ID NO: 54) and n is greater than 10.
  • L3 is (GGGGS)n (SEQ ID NO: 55) and n is 1. In some embodiments, L3 is (GGGGS)n (SEQ ID NO: 55) and n is 2. In some embodiments, L3 is (GGGGS)n (SEQ ID NO: 55) and n is 3. In some embodiments, L3 is (GGGGS)n (SEQ ID NO: 55) and n is 4. In some embodiments, L3 is (GGGGS)n (SEQ ID NO: 55) and n is 5. In some embodiments, L3 is (GGGGS)n (SEQ ID NO: 55) and n is 6. In some embodiments, L3 is (GGGGS)n (SEQ ID NO: 55) and n is 7.
  • L3 is (GGGGS)n (SEQ ID NO: 55) and n is 8. In some embodiments, L3 is (GGGGS)n (SEQ ID NO: 55) and n is 9. In some embodiments, L3 is (GGGGS)n (SEQ ID NO: 55) and n is 10. In some embodiments, L3 is (GGGGS)n (SEQ ID NO: 55) and n is greater than 10. In some embodiments, L3 is GSAGSAAGSGEF (SEQ ID NO: 56). In some embodiments, L3 is -30- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT KESGSVSSEQLAQFRSLD (SEQ ID NO: 57).
  • L3 is EGKSSGSGSESKST (SEQ ID NO: 58).
  • the flexible peptide linker L3 may be any flexible peptide linker.
  • L3 is selected from the group of flexible linkers including, but not limited to, (GGGGA)n (SEQ ID NO: 54), (GGGGS)n (SEQ ID NO: 55), GSAGSAAGSGEF (SEQ ID NO: 56), KESGSVSSEQLAQFRSLD (SEQ ID NO: 57), EGKSSGSGSESKST (SEQ ID NO: 58), or any combination thereof, wherein each n is, independently, an integer selected from 1-4. In some embodiments, n is 1. In some embodiments, n is 2.
  • n is 3. In some embodiments, n is 4. In some embodiments, L 3 is (GGGGA) n (SEQ ID NO: 54) and n is 1. In some embodiments, L 3 is (GGGGA)n (SEQ ID NO: 54) and n is 2. In some embodiments, L3 is (GGGGA)n (SEQ ID NO: 54) and n is 3. In some embodiments, L3 is (GGGGA)n (SEQ ID NO: 54) and n is 4. In some embodiments, L3 is (GGGGS)n (SEQ ID NO: 55) and n is 1. In some embodiments, L3 is (GGGGS)n (SEQ ID NO: 55) and n is 2.
  • L3 is (GGGGS)n (SEQ ID NO: 55) and n is 3. In some embodiments, L3 is (GGGGS)n (SEQ ID NO: 55) and n is 4. In some embodiments, L3 is GSAGSAAGSGEF (SEQ ID NO: 56). In some embodiments, L3 is KESGSVSSEQLAQFRSLD (SEQ ID NO: 57). In some embodiments, L3 is EGKSSGSGSESKST (SEQ ID NO: 58).
  • L3 is selected from the group of flexible linkers including, but not limited to, (GGGGA)n (SEQ ID NO: 54), (GGGGS)n (SEQ ID NO: 55), GSAGSAAGSGEF (SEQ ID NO: 56), KESGSVSSEQLAQFRSLD (SEQ ID NO: 57), EGKSSGSGSESKST (SEQ ID NO: 58), or any combination thereof, wherein each n is, independently, an integer selected from 1, 2, or 4. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 4. In some embodiments, L3 is (GGGGA)n (SEQ ID NO: 54) and n is 1.
  • L3 is (GGGGA)n (SEQ ID NO: 54) and n is 2. In some embodiments, L3 is (GGGGA)n (SEQ ID NO: 54) and n is 4. In some embodiments, L3 is (GGGGS)n (SEQ ID NO: 55) and n is 1. In some embodiments, L3 is (GGGGS)n (SEQ ID NO: 55) and n is 2. In some embodiments, L3 is (GGGGS)n (SEQ ID NO: 55) and n is 4. In some embodiments, L3 is GSAGSAAGSGEF (SEQ ID NO: 56). In some embodiments, L3 is KESGSVSSEQLAQFRSLD (SEQ ID NO: 57).
  • L3 is EGKSSGSGSESKST (SEQ ID NO: 58).
  • X1 comprises a polypeptide having a formula of ECD-TM- ICD, wherein ECD is an extracellular domain, or a fragment thereof, of a cell surface protein, or is absent; TM is a transmembrane domain of a transmembrane protein; and ICD is an -31- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT intracellular domain of a protein or a protein that facilitates the incorporation of the targeting moiety into the envelope of the viral particle, or is absent.
  • the targeting moiety comprising the formula T-S1 that may also be given by the formula T-L3- X1, may also be given by the formula T-L3- ECD-TM-ICD, wherein T is a target binding domain, L3 is a flexible peptide linker ECD is an extracellular domain, or a fragment thereof, of a cell surface protein, or is absent; TM is a transmembrane domain of a transmembrane protein; and ICD is an intracellular domain of a protein or a protein that facilitates the incorporation of the targeting moiety into the envelope of the viral particle, or is absent.
  • the stalk portion S1 may be given by the formula L 3 - ECD-T M -ICD.
  • the ECD is absent.
  • the ECD can be any appropriate extracellular domain or fragment thereof.
  • the ECD is from a different protein as compared to the transmembrane domain.
  • the ECD domain can be the entire ECD domain or a fragment thereof.
  • the ECD domain is a CD8 or CD28 ECD domain, or a fragment thereof.
  • the ECD domain is a CD8 ECD domain or fragment thereof.
  • the CD8 ECD domain comprises the polypeptide of FVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD (SEQ ID NO: 59). In some embodiments, the CD8 ECD domain consists or consists essentially of the polypeptide of FVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD (SEQ ID NO: 59). In some embodiments, the ECD domain comprises a polypeptide that is 25-45 amino acids in length.
  • the ECD comprises a polypeptide that is at least, or is about, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a peptide of FVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD (SEQ ID NO: 59).
  • the ECD domain is a CD28 ECD domain or fragment thereof.
  • the CD28 ECD domain comprises the polypeptide of KIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP (SEQ ID NO: 60).
  • the CD28 ECD domain consists or consists essentially of the polypeptide of KIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP (SEQ ID NO: 60).
  • the ECD domain comprises a polypeptide that is 25-45 amino acids in length.
  • the ECD comprises a polypeptide that is at least, or is about, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a peptide of KIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP (SEQ ID NO: 60).
  • the TM can be any appropriate transmembrane domain or fragment thereof.
  • the TM domain is a CD8 or CD28 TM domain or a fragment thereof.
  • the TM domain is a CD8 TM domain or fragment thereof.
  • the CD8 TM domain comprises the polypeptide of IYIWAPLAGTCGVLLLSLVITLYCNHRN (SEQ ID NO: 61).
  • the CD8 TM domain consists or consists essentially of the polypeptide of IYIWAPLAGTCGVLLLSLVITLYCNHRN (SEQ ID NO: 61).
  • the TM comprises a polypeptide that is at least, or is about, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a peptide of IYIWAPLAGTCGVLLLSLVITLYCNHRN (SEQ ID NO: 61).
  • the T M domain is a CD28 T M domain or fragment thereof.
  • the CD28 TM domain comprises the polypeptide of FWVLVVVGGVLACYSLLVTVAFIIFWV (SEQ ID NO: 62).
  • the CD28 TM domain consists or consists essentially of the polypeptide of FWVLVVVGGVLACYSLLVTVAFIIFWV (SEQ ID NO: 62).
  • the TM comprises a polypeptide that is at least, or is about, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a peptide of FWVLVVVGGVLACYSLLVTVAFIIFWV (SEQ ID NO: 62).
  • the TM domain is from the same protein as the ECD. In some embodiments, the TM domain is from a different protein as the ECD.
  • the TM domain is a CD8, or CD28 TM domain or a fragment thereof and the ECD domain is a CD8, or CD28 ECD domain or fragment thereof.
  • the TM domain is at least, or is about, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a peptide of IYIWAPLAGTCGVLLLSLVITLYCNHRN (SEQ ID NO: 61) and the ECD domain is at least, or is about, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a peptide of FVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD (SEQ ID NO: 59).
  • the TM domain is at least, or is about, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a peptide of IYIWAPLAGTCGVLLLSLVITLYCNHRN (SEQ ID NO: 61) and the ECD domain is at least, or is about, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a peptide of KIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP (SEQ ID NO: 60).
  • the TM domain is at least, or is about, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a peptide of FWVLVVVGGVLACYSLLVTVAFIIFWV (SEQ ID NO: 62) and the ECD domain is at least, or is about, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a peptide of -33- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT FVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD (SEQ ID NO: 59).
  • the TM domain is at least, or is about, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a peptide of FWVLVVVGGVLACYSLLVTVAFIIFWV (SEQ ID NO: 62) and the ECD domain is at least, or is about, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a peptide of KIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP (SEQ ID NO: 60).
  • the transmembrane domain is linked to an intracellular domain (ICD) of a cellular transmembrane protein, or a fragment thereof.
  • ICD intracellular domain
  • the ICD is absent.
  • the ICD is from the same or different protein as the TM domain.
  • the ICD comprises an Env incorporation motif.
  • An Env incorporation motif is a molecule, e.g., polypeptide, that can help to facilitate the incorporation of a protein into the envelope of the virus.
  • a non-limiting example of an Env incorporation motif is a polypeptide comprising the amino acid sequence of NRVRQGYS (SEQ ID NO: 63).
  • the Env incorporation motif comprises an amino acid sequence of SEQ ID NO: 63, SEQ ID NO: 64, or a combination thereof. In some embodiments, the Env incorporation motif comprises an amino acid sequence of SEQ ID NO: 63. In some embodiments, the Env incorporation motif comprises an amino acid sequence of SEQ ID NO: 64.
  • the target binding domain “T” is any polypeptide or polynucleotide that may be used to bind to a desired target.
  • T is any polypeptide, polynucleotide, or fragment thereof that binds to CD7, CD8, cKit (CD117), CD4, CD3, CD5, CD6, CD2, TCR alpha, TCR beta, TCR gamma, TCR delta, CD10, CD34, CD110, CD33, CD14, CD68, CCR7, CD62L, CD25, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, or CXCR3,
  • the targeting moiety “T” binds to CD7. In some embodiments, the target binding domain “T” binds to CD8. In some embodiments, the target binding domain “T” is an antibody. It is to be -36- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT understood that in the context of the present disclosure “antibody” not only refers to a “complete” antibody comprising two identical heavy chains, two identical light chains, and two antigen binding fragments, but also refers to antibodies of any isotype, fragments of antibodies including, but not limited to, Fab, Fv, scFv, and Fd fragments, chimeric antibodies, humanized antibodies, single chain antibodies (scAb), single domain antibodies (dAb), single domain heavy chain antibodies, single domain light chain antibodies, bi-specific antibodies, multi-specific antibodies, and fusion proteins comprising an antigen-binding portion of an antibody and a non-antibody protein.
  • the antibody is selected from the group comprising a scFv, Fab, VHH, single domain antibody, and the like. In some embodiments, the antibody is a scFv. In some embodiments the antibody is a Fab. In some embodiments, the antibody is a VHH. In some embodiments, the antibody is a single domain antibody.
  • the viral particles provided for herein are pseudotyped viral particles. In some embodiments, the viral particles are pseudotyped using viral glycoproteins of viruses of the Paramyxoviridae family. In some embodiments, the pseudotyped viral-like particles are pseudotyped using viral glycoproteins of morbillivirus, such as Measles virus.
  • the pseudotyped viral-like particles are pseudotyped using viral glycoproteins of the Measles virus. In some embodiments, the pseudotyped viral-like particles are pseudotyped using viral glycoproteins of henipavirus, such as Nipah virus, Cedar virus, or Hendra virus. In some embodiments, the pseudotyped viral-like particles are pseudotyped using viral glycoproteins of the Nipah virus. In some embodiments, a polypeptide or an antibody as provided herein is linked via a linker to an envelope glycoprotein G or H of a virus of the Paramyxoviridae family. In some embodiments, the virus of the Paramyxoviridae family is a morbillivirus, such as Measles virus.
  • the virus of the Paramyxoviridae family is a henipavirus, such as Nipah virus, Cedar virus, or Hendra virus.
  • the viruses can be pseudotyped with a VSV-G protein, either wild-type or mutant of the same.
  • the mutant VSV-G protein that can be used to pseudotype a virus e.g. lentivirus
  • the mutant VSV-G protein comprising a mutation at position 182 can be used to pseudotype a virus and transduce a cell when the virus comprises a targeting moiety. This mutation inhibits or reduces the VSV-G affinity to its natural co- receptor, the LDL-R.
  • VSV-G proteins as provided can be used, in some embodiments, to transduce a target cell and deliver a heterologous molecule to the targeted cells.
  • a VSV-G protein is provided that comprises a mutation at position 198 as compared to SEQ ID NO: 1 or at position 182 as compared to SEQ ID NO: 2.
  • SEQ ID NO: 1 is the full length protein and SEQ ID NO: 2 is the ectodomain of the VSV-G protein.
  • the 16-mer signal peptide of MKCLLYLAFLFIGVNC (SEQ ID NO: 65) as shown at the N-terminus of SEQ ID NO: 1 is cleaved leaving a protein of SEQ ID NO: 2.
  • SEQ ID NO: 65 The 16-mer signal peptide of MKCLLYLAFLFIGVNC as shown at the N-terminus of SEQ ID NO: 1 is cleaved leaving a protein of SEQ ID NO: 2.
  • SEQ ID NO: 65 The 16-mer signal peptide of MKCLLYLAFLFIGVNC as shown at the N-terminus of SEQ ID NO: 1 is cleaved leaving a protein of SEQ ID NO: 2.
  • the mutation inhibits or decreases the binding of the VSV-G protein to the LDL receptor (LDL-R).
  • the mutation is a I182D mutation as compared to SEQ ID NO: 2.
  • the mutation is a I182E mutation as compared to SEQ ID NO: 2.
  • a VSV-G protein is provided that comprises a mutation at position 198 as compared to SEQ ID NO: 10 or at position 182 as compared to SEQ ID NO: 11.
  • SEQ ID NO: 10 is the full length protein and SEQ ID NO: 11 is the ectodomain of the VSV-G protein.
  • the 16-mer signal peptide of MLSYLIFALVVSPILG (SEQ ID NO: 66) as shown at the N-terminus of SEQ ID NO: 10 is cleaved leaving a protein of SEQ ID NO: 11.
  • the mutation inhibits or decreases the binding of the VSV-G protein to the LDL receptor (LDL-R).
  • LDL-R LDL receptor
  • the mutation is a T182D mutation as compared to SEQ ID NO: 11.
  • the mutation is a T182E mutation as compared to SEQ ID NO: 11.
  • a VSV-G protein that comprises a mutation at position 198 as compared to SEQ ID NO: 12 or at position 182 as compared to SEQ ID NO: 13.
  • SEQ ID NO: 12 is the full length protein and SEQ ID NO: 13 is the ectodomain of the VSV-G protein.
  • the 16-mer signal peptide of MLRLFLFCFLALGAHS (SEQ ID NO: 67) as shown at the N-terminus of SEQ ID NO: 12 is cleaved leaving a protein of SEQ ID NO: 13.
  • the mutation inhibits or decreases the binding of the VSV-G protein to the LDL receptor (LDL-R).
  • LDL-R LDL receptor
  • the mutation is a A182D -38- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT mutation as compared to SEQ ID NO: 13.
  • the mutation is a A182E mutation as compared to SEQ ID NO: 13.
  • a VSV-G protein that comprises a mutation at position 203 as compared to SEQ ID NO: 14 or at position 182 as compared to SEQ ID NO: 15.
  • SEQ ID NO: 14 is the full length protein and SEQ ID NO: 15 is the ectodomain of the VSV-G protein.
  • the 21-mer signal peptide of MKMKMVIAGLILCIGILPAIG (SEQ ID NO: 68) as shown at the N-terminus of SEQ ID NO: 14 is cleaved leaving a protein of SEQ ID NO: 15.
  • the mutation inhibits or decreases the binding of the VSV-G protein to the LDL receptor (LDL-R).
  • LDL-R LDL receptor
  • the mutation is a V182D mutation as compared to SEQ ID NO: 15.
  • the mutation is a V182E mutation as compared to SEQ ID NO: 15.
  • a VSV-G protein that comprises a mutation at position 199 as compared to SEQ ID NO: 16 or at position 182 as compared to SEQ ID NO: 17.
  • SEQ ID NO: 16 is the full length protein and SEQ ID NO: 17 is the ectodomain of the VSV-G protein.
  • the 17-mer signal peptide of MTPAFILCMLLAGSSWA (SEQ ID NO: 69) as shown at the N-terminus of SEQ ID NO: 16 is cleaved leaving a protein of SEQ ID NO: 17.
  • the mutation inhibits or decreases the binding of the VSV-G protein to the LDL receptor (LDL-R).
  • LDL-R LDL receptor
  • the mutation is a V182D mutation as compared to SEQ ID NO: 17.
  • the mutation is a V182E mutation as compared to SEQ ID NO: 17.
  • a VSV-G protein that comprises a mutation at position 199 as compared to SEQ ID NO: 18 or at position 182 as compared to SEQ ID NO: 19.
  • SEQ ID NO: 18 is the full length protein and SEQ ID NO: 19 is the ectodomain of the VSV-G protein.
  • the 17-mer signal peptide of MNFLLLTFIVLPLCSHA (SEQ ID NO: 70) as shown at the N-terminus of SEQ ID NO: 18 is cleaved leaving a protein of SEQ ID NO: 19.
  • the mutation inhibits or decreases the binding of the VSV-G protein to the LDL receptor (LDL-R).
  • LDL-R LDL receptor
  • the mutation is a V182D mutation as compared to SEQ ID NO: 19.
  • the mutation is a V182E mutation as compared to SEQ ID NO: 19.
  • a VSV-G protein that comprises a mutation at position 199 as compared to SEQ ID NO: 20 or at position 182 as compared to SEQ ID NO: 21.
  • SEQ ID NO: 20 is the full length protein and SEQ ID NO: 21 is the ectodomain of the VSV-G protein.
  • the 17-mer signal peptide of MLVLYLLLSLLALGAQC (SEQ ID NO: 71) as shown at the N-terminus of SEQ ID NO: 20 is cleaved leaving a protein of SEQ ID NO: 21.
  • the mutation inhibits or decreases the binding of the VSV-G protein to the LDL receptor (LDL-R).
  • LDL-R LDL receptor
  • the mutation is a I182D mutation as compared to SEQ ID NO: 21.
  • the mutation is a I182E mutation as compared to SEQ ID NO: 21.
  • a polypeptide when said to have a mutation as compared to a reference sequence, such comparison is based on an alignment such as using BlastP or ClustalW or ClutalOmega alignment software using default parameters.
  • position 182 can be found in SEQ ID NO: 2 and also as compared to the other strains as illustrated in FIG.3.
  • FIG.3 illustrates a clustal alignment of the wild-type sequences of the ectodomains of the various strains of the VSV-G protein.
  • the residue that is bolded and underlined are the residues that align to position 182 of SEQ ID NO: 2 of the various strains.
  • SEQ ID NO: 2 refers to ectodomain of the VSV-G protein of the Indiana strain.
  • SEQ ID NO: 11 refers to ectodomain of the VSV-G protein of the New Jersey strain.
  • SEQ ID NO: 13 refers to ectodomain of the VSV-G protein of the Marraba strain.
  • SEQ ID NO: 15 refers to ectodomain of the VSV-G protein of the Carajas strain.
  • SEQ ID NO: 17 refers to ectodomain of the VSV- G protein of the Alagoa strain.
  • SEQ ID NO: 19 refers to ectodomain of the VSV-G protein of the Cocal strain.
  • SEQ ID NO: 21 refers to ectodomain of the VSV-G protein of the Morreton strain.
  • the residue that aligns to residues 182 as compared to SEQ ID NO: 2 can also be mutated as provided for herein.
  • the mutation at position 182 as compared to SEQ ID NO: 2 is not an alanine.
  • the mutation at position 182 as compared to SEQ ID NO: 2 is not a valine.
  • -40- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT In some embodiments, the mutation at position 182 as compared to SEQ ID NO: 2 is I182S, I182H, I182T, I182Q, or I182N.
  • the mutation at position 182 as compared to SEQ ID NO: 11 is T182S, T182H, T182Q, or T182N.
  • the mutation at position 182 as compared to SEQ ID NO: 13 is A182S, A182H, A182T, A182Q, or A182N.
  • the mutation at position 182 as compared to SEQ ID NO: 15 is V182S, V182H, V182T, V182Q, or V182N.
  • the mutation at position 182 as compared to SEQ ID NO: 17 is V182S, V182H, V182T, V182Q, or V182N.
  • the mutation at position 182 as compared to SEQ ID NO: 19 is V182S, V182H, V182T, V182Q, or V182N. In some embodiments, the mutation at position 182 as compared to SEQ ID NO: 21 is I182S, I182H, I182T, I182Q, or I182N. In some embodiments, the mutation at position 182 is not a hydrophobic residue. In some embodiments, the mutation at position 182 is a charged residue. In some embodiments, the mutation at position 182 is a negatively charged residue.
  • the mutations may be described in reference to SEQ ID NO: 1 or SEQ ID NO: 2, which is the VSV-G protein from the Indiana strain, the mutation can also be used in other strains of the VSV-G protein.
  • the mutation can be made in the New Jersey Strain of VSV-G, the Marraba strain of VSV-G, the Carajas strain of VSV-G, the Alagoa strain of VSV-G, the Cocal strain of VSV-G, or the Morreton strain of VSV-G.
  • the sequences of each are as provided herein. Examples of these can be found, for example in U.S. Patent Application Publication No. 20200216502, which is hereby incorporated by reference.
  • the wild-type full length or ectodomain of the New Jersey Strain of VSV-G are SEQ ID NO: 10 and SEQ ID NO: 11, respectively
  • the wild-type full length or ectodomain of Marraba strain of VSV-G are SEQ ID NO: 12 and SEQ ID NO: 13, respectively
  • the wild-type full length or ectodomain of Carajas strain of VSV-G are SEQ ID NO: 14 and SEQ ID NO: 15, respectively
  • the wild-type full length or ectodomain of Alagoa strain of VSV-G are SEQ ID NO: 16 and SEQ ID NO: 17, respectively
  • the wild-type full length or ectodomain of Cocal strain of VSV-G are SEQ ID NO: 18 and SEQ ID NO: 19, respectively
  • the wild-type full length or ectodomain of Morreton strain of VSV-G are SEQ ID NO: 20 and SEQ ID NO: 21, respectively.
  • a VSV-G protein comprising a mutation at position 182 as compared to SEQ ID NO: 2 can also comprise other mutations, such as those described in U.S. Patent Application Publication No. 20200216502, which is hereby incorporated by reference in its entirety.
  • the VSV-G protein can comprise a mutation at a position that corresponds to positions of 8, 47, 209 and/or 354 of SEQ ID NO: 2.
  • the substitution at position 8 is by any amino acid different from the amino acid indicated at that position in the sequence SEQ ID NO: 2, except Y.
  • the substitution at position 209 is by any amino acid different from the amino acid indicated at that position in the sequence SEQ ID NO: 2, except H.
  • the substitution at position 47 is by any amino acid different from the amino acid indicated at that position in the sequence SEQ ID NO: 2, except K or R.
  • the substitution at position 354 is by any amino acid different from the amino acid indicated at that position in the sequence SEQ ID NO: 2, except K or R.
  • the substitution is at position 47 or at position 354, or at both positions 47 and 354 are substituted by A, G, F or Q.
  • the substitution is A or Q.
  • the substitution at position 8 is an alanine, i.e., H8A.
  • the substitution at position 47 is Q or N, i.e., K47Q or K47N.
  • the protein comprises a mutation (substitution) at position 10.
  • the substitution/mutation is Q10A, Q10R, or Q10K.
  • a protein comprising a mutation at position 182 as compared to SEQ ID NO: 2 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 2 (or SEQ ID NO: 1 if using the full length protein).
  • the polypeptide comprises a I182D or I182E mutation.
  • the VSV-G protein comprises a I182S, I182H, I182T, I182Q, or I182N mutation.
  • a protein comprising a mutation at position 182 as compared to SEQ ID NO: 11 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 11 (or SEQ ID NO: 10 if using the full length protein).
  • the polypeptide comprises a T182D or T182E mutation.
  • the VSV-G protein comprises a T182S, T182H, T182Q, or T182N mutation.
  • a protein comprising a mutation at position 182 as compared to SEQ ID NO: 13 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 13 (or SEQ ID NO: 12 if using the full length protein).
  • the polypeptide comprises a A182D or A182E mutation.
  • the VSV-G protein comprises a A182S, A182H, A182T, A182Q, or A182N mutation.
  • a protein comprising a mutation at position 182 as compared to SEQ ID NO: 15 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 15 (or SEQ ID NO: 14 if using the full length protein).
  • the polypeptide comprises a V182D or V182E mutation.
  • the VSV-G protein comprises a V182S, V182H, V182T, V182Q, or V182N mutation.
  • a protein comprising a mutation at position 182 as compared to SEQ ID NO: 17 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 17 (or SEQ ID NO: 16 if using the full length protein).
  • the polypeptide comprises a V182D or V182E mutation.
  • the VSV-G protein comprises a V182S, V182H, V182T, V182Q, or V182N mutation.
  • a protein comprising a mutation at position 182 as compared to SEQ ID NO: 19 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 19 (or SEQ ID NO: 18 if using the full length protein).
  • the polypeptide comprises a V182D or V182E mutation.
  • the VSV-G protein comprises a V182S, V182H, V182T, V182Q, or V182N mutation.
  • a protein comprising a mutation at position 182 as compared to SEQ ID NO: 21 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 21 (or SEQ ID NO: 20 if using the full length protein).
  • the polypeptide comprises a I182D or I182E mutation.
  • the VSV-G protein comprises a I182S, I182H, I182T, I182Q, or I182N mutation.
  • Viral Glycoproteins The mutant VSV-G proteins can be used, for example, to pseudotype a virus, such as, but not limited to a lentivirus. Accordingly, in some embodiments, a viral particle comprising -43- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT a mutant VSV-G protein as provided herein are provided.
  • the viral particle comprises a VSV-G protein comprising a mutation at position 198 as compared to SEQ ID NO: 1.
  • a protein comprising a mutation at position 182 as compared to SEQ ID NO: 2 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 2 (or SEQ ID NO: 1 if using the full length protein).
  • the polypeptide comprises a I182D or I182E mutation as compared to SEQ ID NO: 2.
  • the VSV-G protein comprises a I182S, I182H, I182T, I182Q, or I182N mutation.
  • the viral particle comprises a VSV-G protein comprising a mutation at position 198 as compared to SEQ ID NO: 10.
  • a protein comprising a mutation at position 182 as compared to SEQ ID NO: 11 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 11 (or SEQ ID NO: 10 if using the full length protein).
  • the polypeptide comprises a T182D or T182E mutation as compared to SEQ ID NO: 11.
  • the VSV-G protein comprises a T182S, T182H, T182Q, or T182N mutation.
  • the viral particle comprises a VSV-G protein comprising a mutation at position 198 as compared to SEQ ID NO: 12.
  • a protein comprising a mutation at position 182 as compared to SEQ ID NO: 13 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 13 (or SEQ ID NO: 12 if using the full length protein).
  • the polypeptide comprises a A182D or A182E mutation as compared to SEQ ID NO: 13.
  • the VSV-G protein comprises a A182S, A182H, A182T, A182Q, or A182N mutation.
  • the viral particle comprises a VSV-G protein comprising a mutation at position 203 as compared to SEQ ID NO: 14.
  • a protein comprising a mutation at position 182 as compared to SEQ ID NO: 15 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 15 (or SEQ ID NO: 14 -44- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT if using the full length protein).
  • the polypeptide comprises a V182D or V182E mutation as compared to SEQ ID NO: 15.
  • the VSV-G protein comprises a V182S, V182H, V182T, V182Q, or V182N mutation.
  • the viral particle comprises a VSV-G protein comprising a mutation at position 199 as compared to SEQ ID NO: 16.
  • a protein comprising a mutation at position 182 as compared to SEQ ID NO: 17 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 17 (or SEQ ID NO: 16 if using the full length protein).
  • the polypeptide comprises a V182D or V182E mutation as compared to SEQ ID NO: 17.
  • the VSV-G protein comprises a V182S, V182H, V182T, V182Q, or V182N mutation.
  • the viral particle comprises a VSV-G protein comprising a mutation at position 199 as compared to SEQ ID NO: 18.
  • a protein comprising a mutation at position 182 as compared to SEQ ID NO: 19 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 19 (or SEQ ID NO: 18 if using the full length protein).
  • the polypeptide comprises a V182D or V182E mutation as compared to SEQ ID NO: 19.
  • the VSV-G protein comprises a V182S, V182H, V182T, V182Q, or V182N mutation.
  • the viral particle comprises a VSV-G protein comprising a mutation at position 199 as compared to SEQ ID NO: 20.
  • a protein comprising a mutation at position 182 as compared to SEQ ID NO: 21 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 21 (or SEQ ID NO: 20 if using the full length protein).
  • the polypeptide comprises a I182D or I182E mutation as compared to SEQ ID NO: 21.
  • the VSV-G protein comprises a I182S, I182H, I182T, I182Q, or I182N mutation. In some embodiments, the VSV-G protein further comprises a mutation at position that corresponds to positions 214 and/or 352 of SEQ ID NO: 2. In some embodiments, the residue that corresponds to position 214 of SEQ ID NO: 2 is T214. In some embodiments, the residue that corresponds to position 352 of SEQ ID NO: is T352. In some embodiments, the -45- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT VSV-G protein comprises mutation that corresponds to T214N mutation as compared to SEQ ID NO: 2.
  • the VSV-G protein comprises mutation that corresponds to T352A mutation as compared to SEQ ID NO: 2.
  • the VSV-G protein comprises a T214N and T352A mutations as compared to SEQ ID NO: 2. These mutations can be combined with any other mutations as provided for herein.
  • the T214N and/or T352A mutations are combined with the I182E or I182D mutations.
  • a VSV-G protein comprises an amino acid sequence of SEQ ID NO: 22 and SEQ ID NO: 23, which combines the I182D or I182E, respectively, with the T214N and T352A mutations.
  • VSV-G Protein_ I196D, T230N and T368A mutations (with leader sequence and adjusted numbering) MKCLLYLAFLFIGVNCKFTIVFPHNQKGNWKNVPSNYHYCPSSSDLN WHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPK YITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQSCGYATVTDAEAVI VQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKV KGLCDSNLDSMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACK MQYCKHWGVRLPSGVWFEMADKDLFAAARFPECPEGSSISAPSQTSV DVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFT IINGTLKYFETRYIR
  • the composition comprises a mutation as described in Hwang et al., Gene Ther 2013 Aug;20(8):807-15. (Epub 2013 Jan 31), which is hereby incorporated by reference in its entirety.
  • the mutations can be. at positions 230, 368, 66, and/or -47- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT 162 that corresponds to SEQ ID NO: 1.
  • the positions will be 16 positions less as compared to SEQ ID NO: 2, when the leader sequence is removed.
  • the mutations at those positions are, for example, T230N, T368A, K66T, S162T, or any combination thereof.
  • the VSV-G protein comprises a T230N and a T368A mutation.
  • the VSV-G polypeptide comprises a K66T, S162T, T230N, and a T368A. These positions are those that correspond to the positions in the full length protein (SEQ ID NO: 1).
  • the VSV-G protein comprises T230N mutation, a T368A mutation, a K66T mutation, a S162T mutation, or any combination thereof.
  • the VSV-G protein further comprises one or more mutations in addition to the mutation that corresponds to position 182 of SEQ ID NO: 2, such as those described in U.S. Patent Application Publication No.
  • the VSV-G protein can further comprise a mutation at a position that corresponds to positions of 8, 47, 209 and/or 354 of SEQ ID NO: 2.
  • the substitution at position 8 is by any amino acid different from the amino acid indicated at that position in the sequence SEQ ID NO: 2, except Y.
  • the substitution at position 209 is by any amino acid different from the amino acid indicated at that position in the sequence SEQ ID NO: 2, except H.
  • the substitution at position 47 is by any amino acid different from the amino acid indicated at that position in the sequence SEQ ID NO: 2, except K or R.
  • the substitution at position 354 is by any amino acid different from the amino acid indicated at that position in the sequence SEQ ID NO: 2, except K or R.
  • the substitution is at position 47 or at position 354, or at both positions 47 and 354 are substituted by A, G, F or Q.
  • the substitution is A or Q.
  • the substitution at position 8 is an alanine, i.e., H8A.
  • the substitution at position 47 is Q or N, i.e., K47Q or K47N.
  • the protein comprises a mutation (substitution) at position 10.
  • the substitution/mutation is Q10A, Q10R, or Q10K.
  • the viruses can be pseudotyped with other viral structural proteins.
  • the viral particle can be pseudotyped with a Spring viremia of carp virus G (SVCV-G) protein and transduce a cell when the virus comprises a targeting moiety.
  • the Spring viremia of carp virus G protein as provided can be used, in some embodiments, to transduce a target cell and deliver a heterologous molecule to the targeted cells.
  • a Spring viremia of carp virus G protein is provided that comprises SEQ ID NO: -48- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT 52.
  • SEQ ID NO: 52 is the full length protein and SEQ ID NO: 53 is the ectodomain of the Spring viremia of carp virus G protein that has the N-terminal signal peptide removed. Accordingly, in some embodiments, the protein comprises an amino acid sequence of SEQ ID NO: 53.
  • the Spring viremia of carp virus G protein can be used, for example, to pseudotype a virus, such as, but not limited to a lentivirus. Accordingly, in some embodiments, a viral particle comprising a Spring viremia of carp virus G protein as provided herein are provided.
  • the viral particle comprises a Spring viremia of carp virus G protein comprising SEQ ID NO: 52 or SEQ ID NO: 53 or sequence that is at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 52 or SEQ ID NO: 53.
  • the targeting moiety can be used to target the viral particle comprising the mutant VSV-G protein or the SVCV-G protein to a cell that expresses the target to which the targeting moiety binds to.
  • the target binding domain is an antibody, a scFv antibody, an antigen -49- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT binding domain, an ankyrin repeat (e.g., DARPIN), a VHH domain antibody, a nanobody, single domain antibody, a FN3 domain, or any combination thereof.
  • the target binding domain can be attached to the viral surface through a variant Fc protein (e.g.
  • the targeting moiety is attached (fused or linked) an envelope glycoprotein G or H of a virus of the Paramyxoviridae family, such as a morbillivirus, such as Measles virus, or a henipavirus, such as Nipah virus, Cedar virus, or Hendra virus.
  • a morbillivirus such as Measles virus
  • a henipavirus such as Nipah virus, Cedar virus, or Hendra virus.
  • the targeting moiety can be attached (fused or linked) to a glycoprotein of a virus of the Rhabdoviridae family, such as a vesicular stomatitis New Jersey virus, a vesicular stomatitis Indiana virus, a vesicular stomatitis Alagoas virus, a vesicular stromatitis Maraba virus, a vesicular stomatitis Carajas virus, Parainfluenza virus, Spodoptera frugiperda rhabdovirus isolate Sf G, Drosophila obscura sigmavirus 10A, Wuhan insect virus 7, Perch virus, or Spring viremia of carp virus.
  • a virus of the Rhabdoviridae family such as a vesicular stomatitis New Jersey virus, a vesicular stomatitis Indiana virus, a vesicular stomatitis Alagoas virus,
  • the VSV protein is the mutated proteins, such as those provided for herein.
  • the targeting moiety is attached to a glycoprotein of a virus of the Filoviridae family, such as Ebola virus or a glycoprotein of a virus of the Arenaviridae family, such as Machupo virus.
  • the target binding domain is a scFv.
  • the target binding domain is a single domain antibody.
  • the target binding domain is a VHH.
  • the targeting moiety binds to CD7, CD8, cKit (CD117), CD4, CD3, CD5, CD6, CD2, TCR alpha, TCR beta, TCR gamma, TCR delta, CD10, CD34, CD110, CD33, CD14, CD68, CCR7, CD62L, CD25, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, or CXCR3,
  • the targeting moiety binds to CD7. In some embodiments, the targeting moiety binds to CD8. In some embodiments, the targeting moiety binds to a target that is present on a cell, such as an immune cell.
  • the cell is an immune cell, such as, but not limited to, T cell, B cell; NK cell, dendritic cell, neutrophils, macrophages, a cancer cell; or, -52- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT for example, CD3+ T cell; CD4+ T cell; CD7+ T cell, CD8+ T cell; CD19+ B cell; CD19+ cancer cell; CD20+ B cell; CD20+ cancer cell; CD30+ lung epithelial cell; CD34+ haematopoietic stem cell; CD105+ endothelial cell; CD105+ haematopoietic stem cell; CD117+ haematopoietic stem cell; CD133+
  • the cell is a T cell. In some embodiments, the cell is a B cell. In some embodiments, the cell is a CD7+ T cell and/or CD8+ T cell.
  • CD7 binding polypeptides In some embodiments, the targeting moiety (e.g. polypeptide) binds to CD7. In some embodiments, the polypeptide that binds to CD7 is an antibody which binds to non-human primate CD7. In some embodiments, the polypeptide that binds to CD7 is an antibody which binds to human CD7.
  • the sequence of human CD7 (UniProtKB P09564) is as follows (SEQ ID NO: 29): MAGPPRLLLLPLLLALARGLPGALAAQEVQQSPHCTTVPVGASVNITCSTSGG LRGIYLRQLGPQPQDIIYYEDGVVPTTDRRFRGRIDFSGSQDNLTITMHRLQLS DTGTYTCQAITEVNVYGSGTLVLVTEEQSQGWHRCSDAPPRASALPAPPTGS ALPDPQTASALPDPPAASALPAALAVISFLLGLGLGVACVLARTQIKKLCSWR DKNSAACVVYEDMSHSRCNTLSSPNQYQ (SEQ ID NO: 29).
  • the CD7 that the polypeptide binds to is expressed on the surface of a cell.
  • the cell is an immune cell.
  • the immune cell is a CD7+ T cell, CD4+ T cell, CD8+ T cell, NK cell, alpha-beta T cell, gamma- delta T cell, lymphoid progenitor cell, hematopoietic stem cell, myeloid cell, monocyte, macrophage, central memory T cell, effector memory T cell, stem-cell like memory T cells, na ⁇ ve T cell, activated T cell, regulatory T cell (TReg), terminally differentiated effector memory T cell (TEMRA), resident memory T cell (TRM) or a T-cellCD8+CCR7+.
  • TReg regulatory T cell
  • TEMRA terminally differentiated effector memory T cell
  • TRM resident memory T cell
  • the antibody comprises a Fc region.
  • the Fc region can be linked to the heavy or light chain of the antibody.
  • the Fc region is an IgG Fc.
  • the IgG is selected from IgG1, IgG2, IgG3, or IgG4.
  • the IgG fc is IgG1 Fc.
  • the antibody comprises an Fc constant region as set forth herein, such as SEQ ID NO: 26, 27, or 28 or a mutant thereof as provided for herein. -53- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT
  • polypeptides e.g. CD7-binding polypeptide are provided herein.
  • antibodies e.g. an anti-CD7 antibody
  • the antibody is a recombinant antibody that binds to CD7.
  • the CD7 protein is a human CD7 protein.
  • the CD7 protein is a non-human CD7 protein (e.g., mouse, rat, pig, dog, non-human primate).
  • the term “recombinant antibody” refers to an antibody that is not naturally occurring. In some embodiments, the term “recombinant antibody” refers to an antibody that is not isolated from a human subject.
  • an antibody, or antigen binding fragment thereof comprises a peptide selected from the following table, which illustrate the CDRs based on Chothia numbering. Chothia CDRs Ab ID No HCDR1 HCDR2 HCDR3 LCDR1 LCDR2 LCDR3 T
  • a polypeptide, an antibody, or antibody binding fragment thereof comprises a heavy or light chain CDR as provided in the tables above.
  • a polypeptide, an antibody, or antibody binding fragment thereof comprises a heavy or light chain CDR as provided in the tables above and binds to non-human primate CD7.
  • a polypeptide, an antibody, or antibody binding fragment thereof comprises a heavy or light chain CDR as provided in the tables above and binds to human CD7.
  • a polypeptide, an antibody, or antibody binding fragment thereof comprises a light chain CDR having a sequence selected from SEQ ID NO: 33-35.
  • a polypeptide, an antibody, or antibody binding fragment thereof comprises a light chain CDR having a sequence of SEQ ID NO: 33.
  • a polypeptide, an antibody, or antibody binding fragment thereof comprises a light chain CDR having a sequence of SEQ ID NO: 34.
  • a polypeptide, an antibody, or antibody binding fragment thereof comprises a light chain CDR having a sequence of SEQ ID NO: 35. In some embodiments, a polypeptide, an antibody, or antibody binding fragment thereof, comprises a heavy chain CDR having a sequence selected from SEQ ID NO: 30-32. In some embodiments, a polypeptide, an antibody, or antibody binding fragment thereof, comprises a heavy chain CDR having a sequence of SEQ ID NO: 30. In some embodiments, a polypeptide, an antibody, or antibody binding fragment thereof, comprises a heavy chain CDR having a -54- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT sequence of SEQ ID NO: 31.
  • a polypeptide, an antibody, or antibody binding fragment thereof comprises a heavy chain CDR having a sequence of SEQ ID NO: 32.
  • the CDRs referenced in the embodiments throughout the present specification can be interchanged with the CDRs that are characterized by different formats, such as Kabat and IMGT.
  • a polypeptide, an antibody, or antibody binding fragment thereof comprises a light chain variable region having a LCDR1, a LCDR2, and a LCDR3, wherein the LCDR1 has a sequence of SEQ ID NO: 33, the LCDR2 has a sequence of SEQ ID NO: 34, and the LCDR3 has a sequence of SEQ ID NO: 35.
  • a polypeptide, an antibody, or antibody binding fragment thereof comprises a heavy chain variable region having a HCDR1, a HCDR2, and a HCDR3, wherein the HCDR1 has a sequence of SEQ ID NO: 30, the HCDR2 has a sequence of SEQ ID NO: 31, and the HCDR3 has a sequence of SEQ ID NO: 32.
  • a polypeptide, an antibody or antibody binding fragment thereof comprises: (i) a light chain having any one of the foregoing recited combinations of LCDR1, LCDR2, and LCDR3 sequences; and (ii) a heavy chain having any one of the foregoing recited combinations of HCDR1, HCDR2, and HCDR3 sequences.
  • a polypeptide, an antibody, or antigen binding fragment thereof comprises: (i) a light chain variable region comprising light chain CDRl, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 33; the light chain CDR2 has the amino acid sequence of SEQ ID NO: 34; and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 35; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 30; the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 31; and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 32; or variants of any of the foregoing
  • the equivalent CDR sequences can be used from the IMGT and Kabat designations.
  • the light chain variable region CDR1 is replaced with any of the other light chain CDR1 sequences.
  • the light chain variable region CDR2 is replaced with any of the other light chain CDR2 sequences.
  • -55- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT the light chain variable region CDR3 is replaced with any of the other light chain CDR3 sequences.
  • the heavy chain variable region CDR1 is replaced with any of the other heavy chain CDR1 sequences.
  • the heavy chain variable region CDR2 is replaced with any of the other heavy chain CDR2 sequences.
  • the heavy chain variable region CDR3 is replaced with any of the other heavy chain CDR3 sequences.
  • the polypeptide comprises a heavy chain variable region peptide having one of the following sequences, or a variant thereof: SEQ ID NO: AB ID NO. Sequence 36 CD7AB1 QVQLQQPGAELVKPGASVKLSCKASGYPFTSYWIHWVKQRPGRGL D , p yp p p g g p p having one of the following sequences, or a variant thereof: SEQ ID NO: AB ID NO.
  • a polypeptide, an antibody, or antigen binding fragment thereof comprises a VH peptide of SEQ ID NO: 36.
  • a polypeptide, an antibody, or antigen binding fragment thereof comprises a VL peptide of SEQ ID NO: 37.
  • a polypeptide, an antibody, or antigen binding fragment thereof comprises a V H peptide and a V L peptide, wherein the wherein the V H peptide comprises a sequence of SEQ ID NO: 36, or a variant thereof; and the VL peptide comprises a sequence of SEQ ID NO: 37, or a variant thereof.
  • a polypeptide, an antibody, or antigen binding fragment thereof comprises a VH peptide and a VL peptide, wherein the wherein the VH peptide comprises a sequence of SEQ ID NO: 36, or a variant thereof; and the VL peptide comprises a sequence of SEQ ID NO: 37, or a variant thereof, and the polypeptide, the antibody, or antigen binding fragment thereof, binds to non-human primate CD7.
  • a polypeptide, an antibody, or antigen binding fragment thereof comprises a VH peptide and a VL peptide, wherein the wherein the VH peptide comprises a sequence of SEQ ID NO: 36, or a variant thereof; and the VL peptide comprises a sequence of SEQ ID NO: 37, or a variant thereof, and the polypeptide, the antibody, or antigen binding fragment thereof, binds to human -56- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT CD7.
  • the VH peptide comprises a sequence of SEQ ID NO: 36; and the VL peptide comprises a sequence of SEQ ID NO: 37.
  • the VH and the VL sequences can be in any format, including, but not limited to an scFv format where the VH and VL regions are linked with a peptide linker.
  • peptide linkers that can be used to link various peptides provided for herein include, but are not limited to: (GGGGS)n (SEQ ID NO: 55), wherein each n is independently 1-5.
  • n is 1.
  • n is 2.
  • n is 3.
  • n is 4.
  • n is 5.
  • the variable regions are not linked with a peptide linker.
  • the polypeptide comprises SEQ ID NO: 36 and SEQ ID NO: 37.
  • the polypeptide, antibodies, or antigen binding fragments thereof can be variants of the sequences.
  • the sequences of the polypeptides or antibodies can be modified to yield human IgG antibodies.
  • the conversion of the sequences provided herein can be modified to yield other types of antibodies.
  • the CDRs can also be linked to other antibodies, proteins, or molecules to create antibody fragments that bind CD7.
  • a polypeptide or an antibody as provided herein is a targeting moiety on the surface of an engineered viral particle.
  • the targeting moiety allows for binding to a target cell.
  • the targeting moiety is a CD7 binding moiety, such as a polypeptide or an antibody as provided herein.
  • the target binding domain (“T”) comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 38: DILLTQSPAILSVSPGERVSFSCRASQSIGTSIHWYQQRTNDSPRLLIKYAS ESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQSNSWPTTFGGGTKL EIKRGGGGSGGGGSGGGGSGGGGGGSQVQLQQPGAELVKPGASVKLSCKASGYP FTSYWIHWVKQRPGRGLEWLGRIDPNSGDTKYNEKFKNKATLTVDKSSTTAY MQLSSLTSEDSAVYYCARSPYYSNDNSMDYWGQGTSVTVSS (SEQ ID NO: 38) or is substantially similar to SEQ ID NO: 38, or is an active fragment of SEQ ID NO
  • the target binding domain (“T”) comprises a sequence that is at least 90% identical to a sequence of SEQ ID NO: 38. In some embodiments, the target binding domain (“T”) comprises a sequence that is at least 95% identical to a sequence of SEQ ID NO: 38. In some embodiments, the target binding domain (“T”) comprises a sequence that is at least 99% identical to a sequence of SEQ ID NO: 38. In some embodiments, the target binding domain -57- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT (“T”) comprises a sequence as set forth in SEQ ID NO: 38. In some embodiments, the target binding domain (“T”) as set forth in SEQ ID NO: 38 is an antibody, or an antigen binding fragment thereof.
  • the target binding domain (“T”) is an anti-CD7 antibody.
  • a polypeptide or an antibody as provided for herein is a targeting moiety on the surface of an engineered viral particle.
  • the engineered viral particle is a pseudotyped viral-like particle.
  • the targeting moiety allows for binding to a target cell.
  • the targeting moiety is a CD7 binding moiety, such as a polypeptide or an antibody as provided herein.
  • the target binding domain (“T”) comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 39. In some embodiments, the target binding domain (“T”) comprises a sequence that is at least 90% identical to a sequence of SEQ ID NO: 39.
  • the target binding domain (“T”) comprises a sequence that is at least 95% identical to a sequence of SEQ ID NO: 39. In some embodiments, the target binding domain (“T”) comprises a sequence that is at least 99% identical to a sequence of SEQ ID NO: 39. In some embodiments, the target binding domain (“T”) comprises a sequence as set forth in SEQ ID NO: 39. In some embodiments, the target binding domain (“T”) as set forth in SEQ ID NO: 39 is an antibody, or an antigen binding fragment thereof. In some embodiments, the target binding domain (“T”) is an anti-CD7 antibody. In some embodiments, the anti-CD7 antibody binds to non-human primate CD7.
  • the anti-CD7 antibody binds to human CD7.
  • CD8 binding polypeptides the targeting moiety (e.g. a polypeptide) can bind to CD8.
  • the polypeptide binds to CD8.
  • the polypeptide binds to CD8-alpha.
  • the polypeptide binds to CD8-beta.
  • the polypeptide binds to CD8 heterodimer.
  • the CD8 -58- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT heterodimer comprises CD8-alpha and CD8-beta subunits.
  • the polypeptide binds to CD8-alpha homodimer.
  • the polypeptide that binds to CD8 is an antibody which binds to non-human primate CD8.
  • the antibody that binds to non-human primate CD8 is an antibody which binds to non-human primate CD8-alpha.
  • the antibody that binds to non-human primate CD8 is an antibody which binds to non-human primate CD8-beta.
  • the antibody that binds to non-human primate CD8 is an antibody which binds to non-human primate CD8-alpha homodimer.
  • the antibody that binds to non-human primate CD8 is an antibody which binds to non-human primate CD8 heterodimer.
  • the polypeptide that binds to CD8 is an antibody which binds to human CD8.
  • the antibody that binds to human CD8 is an antibody which binds to human CD8-alpha.
  • the antibody that binds to human CD8 is an antibody which binds to human CD8-beta.
  • the antibody that binds to human CD8 is an antibody which binds to human CD8-alpha homodimer.
  • the antibody that binds to human CD8 is an antibody which binds to human CD8 heterodimer.
  • the sequence of human CD8-alpha (UniProtKB Q8TAW8) is as follows (SEQ ID NO: 40): MALPVTALLLPLALLLHAARPSQFRVSPLDRTWNLGETVELKCQVLLSNPTS GCSWLFQPRGAAASPTFLLYLSQNKPKAAEGLDTQRFSGKRLGDTFVLTLSD FRRENEGCYFCSALSNSIMYFSHFVPVFLPAKPTTTPAPRPPTPAPTIASQPLSL RPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCNHRNR RRVCKCPRPVVKSGDKPSLSARYV (SEQ ID NO: 40).
  • the sequence of human CD8-beta (UniProtKB Q8TD28) is as follows (SEQ ID NO: 41): MRPRLWLLLAAQLTVLHGNSVLQQTPAYIKVQTNKMVMLSCEAKISLSNMR IYWLRQRQAPSSDSHHEFLALWDSAKGTIHGEEVEQEKIAVFRDASRFILNLT SVKPEDSGIYFCMIVGSPELTFGKGTQLSVVDFLPTTAQPTKKSTLKKRVCRLP RPETQKGPLCSPITLGLLVAGVLVLLVSLGVAIHLCCRRRRARLRFMKQLYK (SEQ ID NO: 41).
  • the CD8 that the polypeptide binds to is expressed on the surface of a cell.
  • the cell is an immune cell.
  • the immune cell is a CD7+ T cell, CD4+ T cell, CD8+ T cell, NK cell, alpha-beta T cell, gamma- delta T cell, lymphoid progenitor cell, hematopoietic stem cell, myeloid cell, monocyte, -59- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT macrophage, central memory T cell, effector memory T cell, stem-cell like memory T cells, na ⁇ ve T cell, activated T cell, regulatory T cell (TReg), terminally differentiated effector memory T cell (TEMRA), resident memory T cell (TRM) or a T-cell CD8+CCR7+.
  • TReg regulatory T cell
  • TEMRA terminally differentiated effector memory T cell
  • TRM resident memory T cell
  • the cell is a CD8+ T cell. In some embodiments, the cell is a CD8+ cell. In some embodiments, the antibody comprises a Fc region. The Fc region can be linked to the heavy or light chain of the antibody. In some embodiments, the Fc region is an IgG Fc. In some embodiments, the IgG is selected from IgG1, IgG2, IgG3, or IgG4. In some embodiments, the IgG Fc is IgG1 Fc. In some embodiments, the antibody comprises an Fc constant region as set forth herein, such as SEQ ID NO: 26, 27, or 28 or a variant thereof. In some embodiments, polypeptides (e.g. CD8-binding polypeptide) are provided herein.
  • polypeptides e.g. CD8-binding polypeptide
  • antibodies e.g. an anti-CD8 antibody
  • the antibody is a recombinant antibody that binds to CD8.
  • the CD8 protein is a human CD8 protein.
  • the CD8 protein is a non-human CD8 protein (e.g., mouse, rat, pig, dog, non-human primate).
  • the term “recombinant antibody” refers to an antibody that is not naturally occurring. In some embodiments, the term “recombinant antibody” refers to an antibody that is not isolated from a human subject.
  • an antibody, or antigen binding fragment thereof comprises a peptide selected from the following table, which illustrate the CDRs based on Chothia numbering. Chothia CDRs Ab ID No HCDR1 HCDR2 HCDR3 LCDR1 LCDR2 LCDR3 T
  • a polypeptide, an antibody, or antibody binding fragment thereof comprises a heavy or light chain CDR as provided in the tables above.
  • a polypeptide, an antibody, or antibody binding fragment thereof comprises a heavy or light chain CDR as provided in the tables above and binds to non-human primate CD8.
  • a polypeptide, an antibody, or antibody binding fragment thereof comprises a heavy or light chain CDR as provided in the tables above and binds to human CD8.
  • a polypeptide, an antibody, or antibody binding fragment thereof comprises a light chain CDR having a sequence selected from SEQ ID NO: 45-47.
  • a polypeptide, an antibody, or antibody binding fragment thereof comprises a light chain CDR having a sequence of SEQ ID NO: 45.
  • a polypeptide, an antibody, or antibody binding fragment thereof comprises a light chain CDR having a sequence of SEQ ID NO: 46.
  • a polypeptide, an antibody, or antibody binding fragment thereof comprises a light chain CDR having a sequence of SEQ ID NO: 47. In some embodiments, a polypeptide, an antibody, or antibody binding fragment thereof, comprises a heavy chain CDR having a sequence selected from SEQ ID NO: 42-44. In some embodiments, a polypeptide, an antibody, or antibody binding fragment thereof, comprises a heavy chain CDR having a sequence of SEQ ID NO: 42. In some embodiments, a polypeptide, an antibody, or antibody binding fragment thereof, comprises a heavy chain CDR having a sequence of SEQ ID NO: 43.
  • a polypeptide, an antibody, or antibody binding fragment thereof comprises a heavy chain CDR having a sequence of SEQ ID NO: 44.
  • the CDRs referenced in the embodiments throughout the present specification can be interchanged with the CDRs that are characterized by different formats, such as Kabat and IMGT.
  • a polypeptide, an antibody, or antibody binding fragment thereof comprises a light chain variable region having a LCDR1, a LCDR2, and a LCDR3, wherein the LCDR1 has a sequence of SEQ ID NO: 45, the LCDR2 has a sequence of SEQ ID NO: 46, and the LCDR3 has a sequence of SEQ ID NO: 47.
  • a polypeptide, an antibody, or antibody binding fragment thereof comprises a heavy chain variable region having a HCDR1, a HCDR2, and a HCDR3, wherein the HCDR1 has a sequence of SEQ ID NO: 42, the HCDR2 has a sequence of SEQ ID NO: 43, and the HCDR3 has a sequence of SEQ ID NO: 44.
  • a polypeptide, an antibody or antibody binding fragment thereof comprises: (i) a light chain having any one of the foregoing recited combinations of LCDR1, LCDR2, and LCDR3 sequences; and (ii) a heavy chain having any one of the foregoing recited combinations of HCDR1, HCDR2, and HCDR3 sequences.
  • the different CDR motifs can be combined in any combination including those not depicted in the table above. For example, the following embodiments are provided as non- limiting examples of such combinations.
  • a polypeptide, an antibody, or antigen binding fragment thereof comprises: (i) a light chain variable region comprising light chain CDRl, CDR2, and -61- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 45; the light chain CDR2 has the amino acid sequence of SEQ ID NO: 46; and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 47; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 42; the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 43; and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 44; or variants of any of the foregoing.
  • the equivalent CDR sequences can be used from the IMGT and Kabat designations.
  • the light chain variable region CDR1 is replaced with any of the other light chain CDR1 sequences.
  • the light chain variable region CDR2 is replaced with any of the other light chain CDR2 sequences.
  • the light chain variable region CDR3 is replaced with any of the other light chain CDR3 sequences.
  • the heavy chain variable region CDR1 is replaced with any of the other heavy chain CDR1 sequences.
  • the heavy chain variable region CDR2 is replaced with any of the other heavy chain CDR2 sequences.
  • the heavy chain variable region CDR3 is replaced with any of the other heavy chain CDR3 sequences.
  • the polypeptide comprises a heavy chain variable region peptide having one of the following sequences, or a variant thereof: SEQ ID NO: AB ID NO. Sequence L D
  • the polypeptide comprises a light chain variable region peptide having one of the following sequences, or a variant thereof: SEQ ID NO: AB ID NO. Sequence G Y
  • a polypeptide, an antibody, or antigen binding fragment thereof comprises a VH peptide of SEQ ID NO: 48.
  • a polypeptide, an antibody, or antigen binding fragment thereof comprises a VL peptide of SEQ ID NO: 49.
  • a polypeptide, an antibody, or antigen binding fragment thereof comprises -62- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT a VH peptide and a VL peptide, wherein the wherein the VH peptide comprises a sequence of SEQ ID NO: 48, or a variant thereof; and the VL peptide comprises a sequence of SEQ ID NO: 49, or a variant thereof.
  • a polypeptide, an antibody, or antigen binding fragment thereof comprises a VH peptide and a VL peptide, wherein the wherein the VH peptide comprises a sequence of SEQ ID NO: 48, or a variant thereof; and the VL peptide comprises a sequence of SEQ ID NO: 49, or a variant thereof, and the polypeptide, the antibody, or antigen binding fragment thereof, binds to non-human primate CD8.
  • a polypeptide, an antibody, or antigen binding fragment thereof comprises a VH peptide and a VL peptide, wherein the wherein the VH peptide comprises a sequence of SEQ ID NO: 48, or a variant thereof; and the V L peptide comprises a sequence of SEQ ID NO: 49, or a variant thereof, and the polypeptide, the antibody, or antigen binding fragment thereof, binds to human CD8.
  • the VH peptide comprises a sequence of SEQ ID NO: 48; and the VL peptide comprises a sequence of SEQ ID NO: 49.
  • the VH and the VL sequences can be in any format, including, but not limited to an scFv format where the VH and VL regions are linked with a peptide linker.
  • peptide linkers that can be used to link various peptides provided for herein include, but are not limited to: (GGGGS)n (SEQ ID NO: 55), wherein each n is independently 1-5.
  • n is 1.
  • n is 2.
  • n is 3.
  • n is 4.
  • n is 5.
  • the variable regions are not linked with a peptide linker.
  • the polypeptide comprises SEQ ID NO: 48 and SEQ ID NO: 49.
  • the polypeptide, antibodies, or antigen binding fragments thereof can be variants of the sequences.
  • the sequences of the polypeptides or antibodies can be modified to yield human IgG antibodies.
  • the conversion of the sequences provided herein can be modified to yield other types of antibodies.
  • the CDRs can also be linked to other antibodies, proteins, or molecules to create antibody fragments that bind CD8.
  • a polypeptide or an antibody as provided herein is a targeting moiety on the surface of an engineered viral particle.
  • the targeting moiety allows for binding to a target cell.
  • the target binding domain (“T”) is a CD8 binding moiety, such as a polypeptide or an antibody as provided herein.
  • the target binding domain comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 50: -63- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT NIVLTQSPASLAVSLGQRATISCRASESVDGFGNSFMNWYQQKPGQSPKLLI YLASNLESGVPARFSGSGSRTDFTLTIDPVEADDAATYYCQQNNEDPYTFGG GTKLEIKRGGGGSGGGGSGGGGSGGGGSEVQLQQSGPELVKPGASVKISCKA SRYTFTDYNLHWVKLSHEKSLEWIGFIYPYNGGTGYNQKFKNKAKLTVDYSS STAYMELRSLTSVDAAVYYCARDHRYNEGVSFDYWGQGTTLTVSS (S
  • the target binding domain (“T”) comprises a sequence that is at least 90% identical to a sequence of SEQ ID NO: 50. In some embodiments, the target binding domain (“T”) comprises a sequence that is at least 95% identical to a sequence of SEQ ID NO: 50. In some embodiments, the target binding domain (“T”) comprises a sequence that is at least 99% identical to a sequence of SEQ ID NO: 50. In some embodiments, the target binding domain (“T”) comprises a sequence as set forth in SEQ ID NO: 50. In some embodiments, the target binding domain (“T”) as set forth in SEQ ID NO: 50 is an antibody, or an antigen binding fragment thereof. In some embodiments, the targeting moiety is an anti-CD8 antibody.
  • a polypeptide or an antibody as provided for herein is a targeting moiety on the surface of an engineered viral particle.
  • the engineered viral particle is a pseudotyped viral-like particle.
  • the targeting moiety allows for binding to a target cell.
  • the target binding domain (“T”) is a CD8 binding moiety, such as a polypeptide or an antibody as provided herein.
  • the target binding domain (“T”) comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 51: EVQLQQSGPELVKPGASVKISCKASRYTFTDYNLHWVKLSHEKSLEWIGFIY PYNGGTGYNQKFKNKAKLTVDYSSSTAYMELRSLTSVDAAVYYCARDHRYNE GVSFDYWGQGTTLTVSSGGGGSGGGGSGGGGSGGGGSNIVLTQSPASLAVSL GQRATISCRASESVDGFGNSFMNWYQQKPGQSPKLLIYLASNLESGVPARFS GSGSRTDFTLTIDPVEADDAATYYCQQNNEDPYTFGGGTKLEIKR (SEQ ID NO: 51) or is substantially similar to SEQ ID NO: 51, or is an active fragment
  • the target binding domain (“T”) comprises a sequence that is at least 90% identical to a sequence of SEQ ID NO: 51. In some embodiments, the target binding domain (“T”) comprises a sequence that is at least 95% identical to a sequence of SEQ ID NO: 51. In some embodiments, the target binding domain (“T”) comprises a sequence that is at least 99% identical to a sequence of SEQ ID NO: 51. In some embodiments, the target binding domain (“T”) comprises a sequence as set forth in SEQ ID NO: 51. In some embodiments, the target -64- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT binding domain (“T”) as set forth in SEQ ID NO: 51 is an antibody, or an antigen binding fragment thereof.
  • the targeting moiety is an anti-CD8 antibody.
  • the anti-CD8 antibody binds to non-human primate CD8.
  • the anti-CD8 antibody binds to human CD8.
  • Targeting moieties comprising an Fc domain
  • the VH and VL polypeptides are linked to a stalk portion S1 comprising an Fc region.
  • the Fc region is as provided for herein.
  • the Fc region is a variant Fc region as provided for herein. Non-limiting mutations in the Fc region are provided for herein.
  • the variant Fc region comprises a sequence that is a variant of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28 as provided for herein.
  • the variant of SEQ ID NO: 26 comprises one or more mutations selected from the group consisting of L234A, L235A, N297A, P329G, I253A, H310A, and H435A as provided for herein.
  • the variant of SEQ ID NO: 27 comprises one or more mutations selected from the group consisting of N297A, P329G, I253A, H310A, and H435A as provided for herein.
  • the variant of SEQ ID NO: 28 comprises one or more mutations selected from the group consisting of S228P, L235E, N297A, P329G, I253A, H310A, and H435A as provided for herein.
  • the heavy chain can be linked to a Fc region.
  • the Fc region further comprises (e.g.linked to) a transmembrane domain.
  • the Fc region further comprising a transmembrane domain has a formula of L1-Fc-L2-X1, wherein L1 is a linker as provided for herein or is absent, Fc is a variant Fc region as provided for herein, L2 is a linker as provided for herein or is absent, and X1 is a polypeptide comprising a transmembrane domain as provided for herein.
  • X1 may comprises a polypeptide having the formula ECD-TM-ICD, wherein ECD is an extracellular domain, or a fragment thereof as provided for herein or is absent, TM is a transmembrane domain as provided for herein, and ICD is an intracellular domain as provided for herein or is absent.
  • ECD include, but are not limited to, a CD8 and/or CD28 extracellular domain as provided for herein.
  • TM include, but are not limited to, a CD8 and/or CD28 transmembrane domain as provided for herein.
  • X1 comprises a TM and the ECD and ICD are absent.
  • X1 comprises an ECD, a TM, and the ICD is absent. In some embodiments, X1 comprises a TM and an ICD and the ECD is absent. In some embodiments, X1 comprises an ECD, a TM, and an ICD. In any of the following embodiments, it is to be understood that the ECD, the -65- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT ICD, or both may be optionally absent.
  • X1 comprises a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD comprising an Env incorporation motif
  • X1 members i) a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD comprising an Env incorporation motif
  • X1 comprises a CD8 and/or CD28 TM and an ICD comprising an Env incorporation motif is understood to encompass the following X1 members: i) a CD8 and/or CD28 T M and an ICD comprising an Env incorporation motif; and ii) a CD8 and/or CD28 TM wherein the ICD is absent.
  • X1 comprises a CD8 and/or CD28 ECD and a CD8 and/or CD28 TM is understood to encompass the following X1 members: i) a CD8 and/or CD28 ECD and a CD8 and/or CD28 TM; and ii) a CD8 and/or CD28 TM wherein the ECD is absent.
  • X1 comprises an ECD, a CD8 and/or CD28 TM, and an ICD
  • X1 members i) an ECD, a CD8 and/or CD28 TM, and an ICD; ii) an ECD, and a CD8 and/or CD28 TM wherein the ICD is absent; iii) a CD8 and/or CD28 TM, and an ICD wherein the ECD is absent; and iv) a CD8 and/or CD28 TM wherein the ECD and the ICD are absent.
  • X1 comprises a CD8 and/or CD28 TM and an ICD is understood to encompass the following X1 members: i) a CD8 and/or CD28 TM and an ICD; and ii) a CD8 and/or CD28 TM wherein the ICD is absent.
  • X1 comprises an ECD and a CD8 and/or CD28 TM is understood to encompass the following X1 members: i) an ECD and a CD8 and/or CD28 TM; and ii) a CD8 and/or CD28 TM wherein the ECD is absent.
  • X1 comprises a CD8 and/or CD28 ECD, a TM, and an ICD. In some embodiments, X1 comprises an ECD, a CD8 and/or CD28 TM, and an ICD. In some embodiments, X1 comprises a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD. In some embodiments, X1 comprises an ECD, a TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein. In some embodiments, X1 comprises a CD8 and/or CD28 ECD, a TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • X1 comprises an ECD, a CD8 and/or CD28 TM, -66- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • X1 comprises a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the VH and VL polypeptides provided herein are linked to a stalk portion (S1) comprising an Fc region as provided for herein.
  • the VH and VL polypeptides provided herein are linked to a stalk portion (S1) comprising an Fc region comprising a transmembrane domain as provided for herein.
  • the Fc region further comprising a transmembrane domain has a formula of L1-Fc-L2-X1, wherein L1 is a linker as provided for herein or is absent, Fc is a variant Fc region as provided for herein, L 2 is a linker as provided for herein or absent, and X 1 is a polypeptide comprising a transmembrane domain as provided for herein.
  • X1 may comprises a polypeptide having the formula ECD-TM-ICD, wherein ECD is an extracellular domain, or a fragment thereof as provided for herein or absent, TM is a transmembrane domain as provided for herein, and ICD is an intracellular domain as provided for herein or absent.
  • the VH and VL polypeptides provided herein are linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD.
  • the VH and VL polypeptides provided herein are linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD.
  • the VH and VL polypeptides provided herein are linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD.
  • the VH and VL polypeptides provided herein are linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the VH and VL polypeptides provided herein are linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the VH and VL polypeptides provided herein are linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the VH and VL polypeptides provided herein are linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the VH and VL polypeptides provided herein linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) -67- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT comprising an ECD, a TM, and an ICD are anchored to the surface of a viral particle, such as those provided for herein.
  • the identities of L1, Fc, L2, ECD, TM, and ICD are as provided for herein.
  • the VH and VL polypeptides bind to an immune cell, such as those provided herein.
  • a VH peptide having a sequence as set forth in SEQ ID NO: 36 and a VL peptide having a sequence as set forth in SEQ ID NO: 37 are linked to an a stalk portion (S1) comprising Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD.
  • VH peptide having a sequence as set forth in SEQ ID NO: 36 and VL peptide having a sequence as set forth in SEQ ID NO: 37 are linked to a stalk portion (S1) comprising an Fc region (L 1 -Fc-L 2 -X 1 ) comprising a CD8 and/or CD28 ECD, a T M , and an ICD.
  • VH peptide having a sequence as set forth in SEQ ID NO: 36 and VL peptide having a sequence as set forth in SEQ ID NO: 37 are linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD.
  • VH peptide having a sequence as set forth in SEQ ID NO: 36 and VL peptide having a sequence as set forth in SEQ ID NO: 37 are linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD.
  • the VH peptide having a sequence as set forth in SEQ ID NO: 36 and VL peptide having a sequence as set forth in SEQ ID NO: 37 are linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the VH peptide having a sequence as set forth in SEQ ID NO: 36 and VL peptide having a sequence as set forth in SEQ ID NO: 37 are linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the VH peptide having a sequence as set forth in SEQ ID NO: 36 and VL peptide having a sequence as set forth in SEQ ID NO: 37 are linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a CD8 and/ or CD28 TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the VH peptide having a sequence as set forth in SEQ ID NO: 36 and VL peptide having a sequence as set forth in SEQ ID NO: 37 are linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the VH peptide having a sequence as set forth in SEQ ID NO: 36 and VL peptide having a sequence as set forth in SEQ ID NO: 37 linked to a stalk portion (S1) comprising an -68- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD are anchored to the surface of a viral particle, such as those provided for herein.
  • the identities of L1, Fc, L2, ECD, TM, and ICD are as provided for herein.
  • the VH and VL polypeptides bind to an immune cell, such as those provided herein.
  • the Fc region further comprising a transmembrane domain has a formula of L1-Fc-L2-X1, wherein L1 is a linker as provided for herein or is Fc is a variant Fc region as provided for herein, L2 is a linker as provided for herein or absent, and X1 is a polypeptide comprising a transmembrane domain as provided for herein.
  • X1 may comprises a polypeptide having the formula ECD-TM-ICD, wherein ECD is an extracellular domain, or a fragment thereof as provided for herein or absent, TM is a transmembrane domain as provided for herein, and ICD is an intracellular domain as provided for herein or absent.
  • the VH peptide comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 36; and the VL peptide comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 37 linked to a stalk portion (S1) comprising an Fc region (L1-Fc- L2-X1) comprising an ECD, a TM, and an ICD are anchored to the surface of a viral particle, such as those provided for herein.
  • the identities of L1, Fc, L2, ECD, TM, and ICD are as provided for herein.
  • the V H and V L polypeptides bind to an immune cell, such as those provided herein.
  • a polypeptide is provided comprising a VH peptide and a VL peptide, wherein the VH peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 36; and the VL peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 37.
  • the polypeptide comprises a VH peptide and a VL peptide, wherein the VH peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 36; and the VL peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 37; provided that the VH peptide and a VL peptide comprises a light chain CDR having a sequence of SEQ ID NO: 33-35; and/or a heavy chain CDR having a sequence of SEQ ID NO: 30-32.
  • the polypeptide comprises a VH peptide and a VL peptide, wherein the VH peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 36; and the VL peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 37; provided that the VH peptide and a VL peptide comprise a light chain CDR1 having a sequence of SEQ ID NO: 33; a light chain CDR2 having a sequence of SEQ ID NO: 34; a light chain CDR3 having a sequence of SEQ ID NO: 35; and/or a heavy chain CDR1
  • the CDRs in the VH or VL chain are as set forth in the combinations provided for herein.
  • the polypeptide comprises a VH peptide and a VL peptide, wherein the VH peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 36; and the VL peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 37; provided that the VL peptide comprises a LCDR1 having a sequence of SEQ ID NO: 33; a LCDR2 having a sequence of SEQ ID NO: 34; and a LCDR3 having a sequence of S
  • the polypeptide comprises a VH peptide and a VL peptide, wherein the VH peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 36; and the VL peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 37; provided that the VL peptide comprises a LCDR1 having a sequence of SEQ ID NO: 33, wherein the LCDR1 comprises at most 1 conservative amino acid substitution, a LCDR2 having a sequence of SEQ ID NO: 34, wherein the LCDR2 comprises at most 1 conservative amino acid substitution, and a LCDR3 having a sequence of
  • the polypeptide comprises a VH peptide and a VL peptide, wherein the VH peptide comprises a sequence of SEQ ID NO: 36 and the VL peptide comprises a sequence of SEQ ID NO: 37.
  • the polypeptide as provided herein binds to non-human primate CD7.
  • the polypeptide as provided herein binds to human CD7.
  • the different polypeptides (VH or VL) described herein can be linked with a peptide linker or not linked with a peptide linker and instead for a continuous -72- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT sequence.
  • the peptide linker comprises a sequence of (GGGGS)n (SEQ ID NO: 55), wherein each n is independently 1-5. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5.
  • the linked peptide format can be represented by a formula of VH-Z-VL or VL-Z-VH, wherein Z is the peptide linker. In some embodiments, Z is (GGGGS)n (SEQ ID NO: 55), wherein each n is independently 1-5. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3.
  • n is 4. In some embodiments, n is 5. In some embodiments, the polypeptide comprising the linked peptide represented by a formula of V L -Z-V H comprises a heavy chain variable region as set forth in SEQ ID NO: 36 linked via a linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 72) to a light chain variable region as set forth in SEQ ID NO: 37.
  • the polypeptide comprising a VL linked via a peptide linker to a VH has the sequence as set forth below, DILLTQSPAILSVSPGERVSFSCRASQSIGTSIHWYQQRTNDSPRLLIKYASESIS GIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQSNSWPTTFGGGTKLEIKRGG GGSGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKLSCKASGYPFTSYW IHWVKQRPGRGLEWLGRIDPNSGDTKYNEKFKNKATLTVDKSSTTAYMQLS SLTSEDSAVYYCARSPYYSNDNSMDYWGQGTSVTVSS (SEQ ID NO: 38).
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 38.
  • the polypeptide comprises a sequence that is at least 90% identical to a sequence of SEQ ID NO: 38.
  • the polypeptide comprises a sequence that is at least 95% identical to a sequence of SEQ ID NO: 38.
  • the polypeptide comprises a sequence that is at least 99% identical to a sequence of SEQ ID NO: 38.
  • the polypeptide comprises a sequence as set forth in SEQ ID NO: 38.
  • the polypeptide as set forth in SEQ ID NO: 38 is an antibody, or an antigen binding fragment thereof.
  • the antibody is an anti-CD7 antibody.
  • the anti-CD7 antibody binds to non- human primate CD7.
  • the anti-CD7 antibody binds to human CD7.
  • the polypeptide comprising the linked peptide represented by a formula of VH-Z-VL comprises a light chain variable region as set forth in SEQ ID NO: 37 linked via a linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 72) to a heavy chain variable region as set forth in SEQ ID NO: 36.
  • the polypeptide comprising a VH linked via a peptide linker to a VL has the sequence as set forth below, -73- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT QVQLQQPGAELVKPGASVKLSCKASGYPFTSYWIHWVKQRPGRGLEWLGRI DPNSGDTKYNEKFKNKATLTVDKSSTTAYMQLSSLTSEDSAVYYCARSPYYS NDNSMDYWGQGTSVTVSSGGGGSGGGGSGGGGSGGGGSDILLTQSPAILSVS PGERVSFSCRASQSIGTSIHWYQQRTNDSPRLLIKYASESISGIPSRFSGSGSGT DFTLSINSVESEDIADYYCQQSNSWPTTFGGGTKLEIKR (SEQ ID NO: 39).
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 39.
  • the polypeptide comprises a sequence that is at least 90% identical to a sequence of SEQ ID NO: 39.
  • the polypeptide comprises a sequence that is at least 95% identical to a sequence of SEQ ID NO: 39.
  • the polypeptide comprises a sequence that is at least 99% identical to a sequence of SEQ ID NO: 39.
  • the polypeptide comprises a sequence as set forth in SEQ ID NO: 39.
  • the polypeptide as set forth in SEQ ID NO: 39 is an antibody, or an antigen binding fragment thereof.
  • the antibody is an anti-CD7 antibody.
  • the anti-CD7 antibody binds to non- human primate CD7.
  • the anti-CD7 antibody binds to human CD7.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region, such as those provided herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region, said Fc region further comprising a transmembrane domain such as those provided herein.
  • the Fc region further comprising a transmembrane domain has a formula of L1-Fc-L2-X1, wherein L1 is a linker as provided for herein or is absent, Fc is a variant Fc region as provided for herein, L2 is a linker as provided for herein or is absent, and X1 is a polypeptide comprising a transmembrane domain as provided for herein.
  • X1 may comprises a polypeptide having the formula ECD-TM-ICD, wherein ECD is an extracellular domain, or a fragment thereof as provided for herein or is absent, TM is a transmembrane domain as provided for herein, and ICD is an intracellular domain as provided for herein or is absent.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region (L1- Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD.
  • S1 stalk portion comprising an Fc region (L1- Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region (L1- Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 38 and comprising a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD, is anchored to the surface of a viral particle, such as those provided for herein .
  • the identities of L1, Fc, L2, ECD, TM, and ICD are as provided for -75- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT herein.
  • the polypeptide bind to an immune cell, such as those provided herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region, such as those provided herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region, said Fc region further comprising a transmembrane domain such as those provided herein.
  • the Fc region further comprising a transmembrane domain has a formula of L1-Fc-L2-X1, wherein L1 is a linker as provided for herein or is absent, Fc is a variant Fc region as provided for herein, L2 is a linker as provided for herein or is absent, and X1 is a polypeptide comprising a transmembrane domain as provided for herein.
  • X1 may comprises a polypeptide having the formula ECD-TM-ICD, wherein ECD is an extracellular domain, or a fragment thereof as provided for herein or absent, TM is a transmembrane domain as provided for herein, and ICD is an intracellular domain as provided for herein or absent.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a -76- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 39 and comprising a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD, is anchored to the surface of a viral particle, such as those provided for herein .
  • the identities of L1, Fc, L2, ECD, TM, and ICD are as provided for herein.
  • the polypeptide bind to an immune cell, such as those provided herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region, such as those provided herein. In some embodiments, the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region, said Fc region further comprising a transmembrane domain, such as those provided herein.
  • the Fc region further comprising a transmembrane domain has a formula of L1-Fc-L2-X1, wherein L1 is a linker as provided for herein or is absent, Fc is a variant Fc region as provided for herein, L2 is a linker as provided for herein or is absent, and X1 is a polypeptide comprising a transmembrane domain as provided for herein.
  • X1 may comprises a polypeptide having the formula ECD-TM-ICD, wherein ECD is an extracellular domain, or a fragment thereof as provided for herein or is absent, TM is a transmembrane domain as provided for herein, and ICD is an intracellular domain as provided for herein or is absent.
  • the polypeptide comprises a sequence having a -77- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT sequence as set forth in SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 T M , and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprising a sequence having a sequence as set forth in SEQ ID NO: 38 and comprising a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD, is anchored to the surface of a viral particle, such as those provided for herein .
  • the identities of L1, Fc, L2, ECD, TM, and ICD are as provided for herein.
  • the polypeptide bind to an immune cell, such as those provided herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region, such as those provided herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region, said Fc region further comprising a transmembrane domain, such as those provided -78- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT herein.
  • the Fc region further comprising a transmembrane domain has a formula of L1-Fc-L2-X1, wherein L1 is a linker as provided for herein or is absent, Fc is a variant Fc region as provided for herein, L2 is a linker as provided for herein or is absent, and X1 is a polypeptide comprising a transmembrane domain as provided for herein.
  • X1 may comprises a polypeptide having the formula ECD-TM-ICD, wherein ECD is an extracellular domain, or a fragment thereof as provided for herein or absent, TM is a transmembrane domain as provided for herein, and ICD is an intracellular domain as provided for herein or absent.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprising a sequence having a sequence as set forth in SEQ ID NO: 39 and comprising a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD, is -79- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT anchored to the surface of a viral particle, such as those provided for herein .
  • the identities of L1, Fc, L2, ECD, TM, and ICD are as provided for herein.
  • the polypeptide bind to an immune cell, such as those provided herein.
  • the polypeptide provided for herein comprising the formula of T-S1, wherein T is a target binding domain and S1 is a stalk portion, comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 98: METDTLLLWVLLLWVPGSTGDSAQVQLQQPGAELVKPGASVKLSCKASGYPFTSYWIHWVKQRPGRGLEWLGRI DPNSGDTKYNEKFKNKATLTVDKSSTTAYMQLSSLTSEDSAVYYCARSPYYSNDNSMDYWGQGTSVTVSSGGGGS GGGGSGGGGSGGSDILLTQSPAILSVSPGERVSFSCRASQSIGTSIHWYQQRTNDSPRLLIKYASESISGIPSRFSG SGSGTDFTLSINSVE
  • the polypeptide provided for herein comprising the formula of T-S1 comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 98. In some embodiments, the polypeptide provided for herein comprising the formula of T- S1 comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 98. In some embodiments, the polypeptide provided for herein comprising the formula of T-S1 comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 98. In some embodiments, the polypeptide provided for herein comprising the formula of T-S1 comprises an amino acid sequence of SEQ ID NO: 98.
  • the targeting moiety comprising a formula of T-S1 comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 167: SAQVQLQQPGAELVKPGASVKLSCKASGYPFTSYWIHWVKQRPGRGLEWLGR IDPNSGDTKYNEKFKNKATLTVDKSSTTAYMQLSSLTSEDSAVYYCARSPYY SNDNSMDYWGQGTSVTVSSGGGGSGGGGSGGGGSGGSDILLTQSPAILSV SPGERVSFSCRASQSIGTSIHWYQQRTNDSPRLLIKYASESISGIPSRFSGS GSGTDFTLSINSVESEDIADYYCQQSNSWPTTFGGGTKLEIKRASGGGGSGG GGSGGGGSEPKSCDKTHTCPPCPAPEAAGGP
  • the targeting moiety comprising a formula of T-S1 comprises an amino acid sequence having 95% identity to SEQ ID NO: 167. In some embodiments, the targeting moiety comprising a formula of T-S1 comprises an amino acid sequence having 98% identity to SEQ ID NO: 167. In some embodiments, the targeting moiety comprising a formula of T-S1 comprises an amino acid sequence of SEQ ID NO: 167.
  • the targeting moiety comprising a formula of T-S1 comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 168: QVQLQQPGAELVKPGASVKLSCKASGYPFTSYWIHWVKQRPGRGLEWLGRID PNSGDTKYNEKFKNKATLTVDKSSTTAYMQLSSLTSEDSAVYYCARSPYYSN DNSMDYWGQGTSVTVSSGGGGSGGGGSGGGGSGGSDILLTQSPAILSVSP GERVSFSCRASQSIGTSIHWYQQRTNDSPRLLIKYASESISGIPSRFSGSGS GTDFTLSINSVESEDIADYYCQQSNSWPTTFGGGTKLEIKRASGGGGSGGGGGG SGGGGSEPKSCDKTHTCPPCPAPEAAGGPSV
  • the targeting moiety comprising a formula of T-S1 comprises an amino acid sequence having 95% identity to SEQ ID NO: 168. In some embodiments, the targeting moiety comprising a formula of T-S1 comprises an amino acid sequence having 98% identity to SEQ ID NO: 168. In some embodiments, the targeting moiety comprising a formula of T-S1 comprises an amino acid sequence of SEQ ID NO: 168.
  • the polypeptide provided for herein comprising the formula of T-S1, wherein T is a target binding domain and S1 is a stalk portion, comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 98, wherein the target binding domain “T” of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98, and -81- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT wherein the stalk portion “S1” of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO: 98.
  • the polypeptide provided for herein comprising the formula of T-S1 comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 98, wherein the target binding domain “T” of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98, and wherein the stalk portion “S1” of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO: 98.
  • the polypeptide provided for herein comprising the formula of T-S1 comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 98, wherein the target binding domain “T” of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98, and wherein the stalk portion “S 1 ” of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO: 98.
  • the polypeptide provided for herein comprising the formula of T-S1 comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 98, wherein the target binding domain “T” of the polypeptide corresponds to amino acids 25- 283 of SEQ ID NO: 98, and wherein the stalk portion “S1” of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO: 98.
  • the polypeptide provided for herein comprising the formula of T-S1 comprises an amino acid sequence of SEQ ID NO: 98, wherein the target binding domain “T” of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98, and wherein the stalk portion “S1” of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO: 98.
  • the polypeptide provided for herein comprising the formula of T-S1, wherein T is a target binding domain comprising a VH and a VL, and S1 is a stalk portion, comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 98, wherein the VH of the target binding domain corresponds to amino acids 25-150 of SEQ ID NO: 98, the VL of the target binding domain corresponds to amino acids 172-283 of SEQ ID NO: 98, and wherein the stalk portion “S1” of the polypeptide corresponds to amino acids 284- 634 of SEQ ID NO: 98.
  • the polypeptide provided for herein comprising the formula of T-S1 comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 98, wherein the VH of the target binding domain corresponds to amino acids 25-150 of SEQ ID NO: 98, the VL of the target binding domain corresponds to amino acids 172-283 of SEQ ID NO: 98, and wherein the stalk portion “S1” of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO: 98.
  • the polypeptide provided for herein comprising the formula of T-S1 comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 98, wherein the VH of the target binding -82- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT domain corresponds to amino acids 25-150 of SEQ ID NO: 98, the VL of the target binding domain corresponds to amino acids 172-283 of SEQ ID NO: 98, and wherein the stalk portion “S1” of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO: 98.
  • the polypeptide provided for herein comprising the formula of T-S1 comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 98, wherein the VH of the target binding domain corresponds to amino acids 25-150 of SEQ ID NO: 98, the VL of the target binding domain corresponds to amino acids 172-283 of SEQ ID NO: 98, and wherein the stalk portion “S1” of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO: 98.
  • the polypeptide provided for herein comprising the formula of T-S 1 comprises an amino acid sequence of SEQ ID NO: 98, wherein the V H of the target binding domain corresponds to amino acids 25-150 of SEQ ID NO: 98, the VL of the target binding domain corresponds to amino acids 172-283 of SEQ ID NO: 98, and wherein the stalk portion “S1” of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO: 98.
  • the polypeptide provided for herein comprising the formula of T-L1-Fc-L2-X1, wherein T is a target binding domain, L1 is a polypeptide linker or is absent, Fc is a variant Fc domain as provided for herein, L2 is a polypeptide linker or is absent, and X1 is a polypeptide comprising a transmembrane domain, comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 98, wherein the target binding domain “T” of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98, L1 comprises amino acids 284-301 of SEQ ID NO: 98, Fc comprises amino acids 302-542 of SEQ ID NO: 98, L2 is absent, and X1 corresponds to amino acids 54
  • the polypeptide provided for herein comprising the formula of T-L1-Fc-L2-X1 comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 98, wherein the target binding domain “T” of the polypeptide corresponds to amino acids 25- 283 of SEQ ID NO: 98, L1 comprises amino acids 284-301 of SEQ ID NO: 98, Fc comprises amino acids 302-542 of SEQ ID NO: 98, L2 is absent, and X1 corresponds to amino acids 543- 634 of SEQ ID NO: 98.
  • the polypeptide provided for herein comprising the formula of T-L1-Fc-L2-X1 comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 98, wherein the target binding domain “T” of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98, L1 comprises amino acids 284-301 of SEQ ID NO: 98, Fc comprises amino acids 302-542 of SEQ ID NO: 98, L2 is absent, and X1 corresponds to amino acids 543-634 of SEQ ID NO: 98.
  • the polypeptide provided for herein comprising the formula of T-L1-Fc-L2-X1 comprises an amino acid -83- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT sequence that is at least 98% identical to a sequence of SEQ ID NO: 98, wherein the target binding domain “T” of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98, L1 comprises amino acids 284-301 of SEQ ID NO: 98, Fc comprises amino acids 302-542 of SEQ ID NO: 98, L2 is absent, and X1 corresponds to amino acids 543-634 of SEQ ID NO: 98.
  • the polypeptide provided for herein comprising the formula of T-L1-Fc- L2-X1 comprises an amino acid sequence of SEQ ID NO: 98, wherein the target binding domain “T” of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98, L1 comprises amino acids 284-301 of SEQ ID NO: 98, Fc comprises amino acids 302-542 of SEQ ID NO: 98, L2 is absent, and X1 corresponds to amino acids 543-634 of SEQ ID NO: 98.
  • the polypeptide provided for herein comprising the formula of T-L1-Fc-L2-X1, wherein T is a target binding domain comprising a VH and a VL, L1 is a polypeptide linker or is absent, Fc is a variant Fc domain as provided for herein, L2 is a polypeptide linker or is absent, and X1 is a polypeptide comprising a transmembrane domain, comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 98, wherein the VH of the target binding domain corresponds to amino acids 25-150 of SEQ ID NO: 98, the VL of the target binding domain corresponds to amino acids 172-283 of SEQ ID NO: 98, L1 comprises amino acids 284-301 of SEQ ID NO: 98, F
  • the polypeptide provided for herein comprising the formula of T-L1-Fc-L2-X1 comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 98, wherein the VH of the target binding domain corresponds to amino acids 25-150 of SEQ ID NO: 98, the VL of the target binding domain corresponds to amino acids 172-283 of SEQ ID NO: 98, L1 comprises amino acids 284-301 of SEQ ID NO: 98, Fc comprises amino acids 302-542 of SEQ ID NO: 98, L2 is absent, and X1 corresponds to amino acids 543-634 of SEQ ID NO: 98.
  • the polypeptide provided for herein comprising the formula of T-L1-Fc-L2-X1 comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 98, wherein the VH of the target binding domain corresponds to amino acids 25-150 of SEQ ID NO: 98, the VL of the target binding domain corresponds to amino acids 172-283 of SEQ ID NO: 98, L1 comprises amino acids 284-301 of SEQ ID NO: 98, Fc comprises amino acids 302-542 of SEQ ID NO: 98, L2 is absent, and X1 corresponds to amino acids 543-634 of SEQ ID NO: 98.
  • the polypeptide provided for herein comprising the formula of T-L1-Fc-L2-X1 comprises an amino acid sequence of SEQ ID NO: 98, wherein the VH of the target binding domain corresponds to amino acids 25-150 of SEQ ID NO: 98, the VL of the target binding domain corresponds to amino acids 172-283 of SEQ ID NO: 98, L1 comprises amino acids 284-301 of SEQ ID NO: 98, Fc comprises amino acids 302-542 of SEQ ID NO: 98, L2 is absent, and X 1 corresponds to amino acids 543-634 of SEQ ID NO: 98.
  • the polypeptide provided for herein comprising the formula of T-L1-Fc-L2-ECD-TM-ICD, wherein T is a target binding domain, L1 is a polypeptide linker or is absent, Fc is a variant Fc domain as provided for herein, L2 is a polypeptide linker or is absent, ECD is an extracellular domain, TM is a transmembrane domain, and ICD is an intracellular domain comprising a env incorporation motif, comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 98, wherein the target binding domain “T” of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98, L1 comprises amino acids 284-301 of SEQ ID NO: 98, Fc comprises amino acids 302-542
  • the polypeptide provided for herein comprising the formula of T-L1-Fc- L2-ECD-TM-ICD comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 98, wherein the target binding domain “T” of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98, L1 comprises amino acids 284-301 of SEQ ID NO: 98, Fc comprises amino acids 302-542 of SEQ ID NO: 98, L2 is absent, ECD comprises amino acids 543-584 of SEQ ID NO: 98, TM comprises amino acids 585-612 of SEQ ID NO: 98, and ICD comprises amino acids 613-634 of SEQ ID NO: 98, wherein the env incorporation motif comprises amino acids 627-634 of SEQ ID NO: 98.
  • the polypeptide provided for herein comprising the formula of T-L1-Fc-L2-ECD-TM-ICD comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 98, wherein the target binding domain “T” of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98, L1 comprises amino acids 284-301 of SEQ ID NO: 98, Fc comprises amino acids 302-542 of -85- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT SEQ ID NO: 98, L2 is absent, ECD comprises amino acids 543-584 of SEQ ID NO: 98, TM comprises amino acids 585-612 of SEQ ID NO: 98, and ICD comprises amino acids 613-634 of SEQ ID NO: 98, wherein the env incorporation motif comprises amino acids 627-634 of SEQ ID NO: 98.
  • the polypeptide provided for herein comprising the formula of T-L1-Fc-L2-ECD-TM-ICD comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 98, wherein the target binding domain “T” of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98, L1 comprises amino acids 284-301 of SEQ ID NO: 98, Fc comprises amino acids 302-542 of SEQ ID NO: 98, L2 is absent, ECD comprises amino acids 543-584 of SEQ ID NO: 98, TM comprises amino acids 585-612 of SEQ ID NO: 98, and ICD comprises amino acids 613-634 of SEQ ID NO: 98, wherein the env incorporation motif comprises amino acids 627-634 of SEQ ID NO: 98.
  • the polypeptide provided for herein comprising the formula of T-L1-Fc- L2-ECD-TM-ICD comprises an amino acid sequence of SEQ ID NO: 98, wherein the target binding domain “T” of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98, L1 comprises amino acids 284-301 of SEQ ID NO: 98, Fc comprises amino acids 302-542 of SEQ ID NO: 98, L2 is absent, ECD comprises amino acids 543-584 of SEQ ID NO: 98, TM comprises amino acids 585-612 of SEQ ID NO: 98, and ICD comprises amino acids 613-634 of SEQ ID NO: 98, wherein the env incorporation motif comprises amino acids 627-634 of SEQ ID NO: 98.
  • the polypeptide provided for herein comprising the formula of T-L1-Fc-L2-ECD-TM-ICD, wherein T is a target binding domain comprising a VH and a VL, L1 is a polypeptide linker or is absent, Fc is a variant Fc domain as provided for herein, L2 is a polypeptide linker or is absent, ECD is an extracellular domain, TM is a transmembrane domain, and ICD is an intracellular domain comprising a env incorporation motif, comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 98, wherein the VH of the target binding domain corresponds to amino acids 25-150 of SEQ ID NO: 98, the VL of the target binding domain corresponds to amino acids 172-283 of SEQ ID NO: 98
  • the polypeptide provided for herein comprising the formula of T-L1-Fc- L2-ECD-TM-ICD comprises an amino acid sequence that is at least 90% identical to a sequence -86- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT of SEQ ID NO: 98, wherein the VH of the target binding domain corresponds to amino acids 25-150 of SEQ ID NO: 98, the VL of the target binding domain corresponds to amino acids 172-283 of SEQ ID NO: 98, L1 comprises amino acids 284-301 of SEQ ID NO: 98, Fc comprises amino acids 302-542 of SEQ ID NO: 98, L2 is absent ECD comprises amino acids 543-584 of SEQ ID NO: 98, TM comprises amino acids 585-612 of SEQ ID NO: 98, and ICD comprises amino acids 613-634 of SEQ ID NO: 98, wherein the env incorporation motif comprises amino acids 627-634 of SEQ ID NO: 98.
  • the polypeptide provided for herein comprising the formula of T-L1-Fc-L2-ECD-TM-ICD comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 98, wherein the VH of the target binding domain corresponds to amino acids 25-150 of SEQ ID NO: 98, the V L of the target binding domain corresponds to amino acids 172-283 of SEQ ID NO: 98, L1 comprises amino acids 284-301 of SEQ ID NO: 98, Fc comprises amino acids 302-542 of SEQ ID NO: 98, L2 is absent ECD comprises amino acids 543-584 of SEQ ID NO: 98, TM comprises amino acids 585-612 of SEQ ID NO: 98, and ICD comprises amino acids 613-634 of SEQ ID NO: 98, wherein the env incorporation motif comprises amino acids 627-634 of SEQ ID NO: 98.
  • the polypeptide provided for herein comprising the formula of T- L1-Fc-L2-ECD-TM-ICD comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 98, wherein the VH of the target binding domain corresponds to amino acids 25-150 of SEQ ID NO: 98, the VL of the target binding domain corresponds to amino acids 172-283 of SEQ ID NO: 98, L1 comprises amino acids 284-301 of SEQ ID NO: 98, Fc comprises amino acids 302-542 of SEQ ID NO: 98, L2 is absent ECD comprises amino acids 543-584 of SEQ ID NO: 98, TM comprises amino acids 585-612 of SEQ ID NO: 98, and ICD comprises amino acids 613-634 of SEQ ID NO: 98, wherein the env incorporation motif comprises amino acids 627-634 of SEQ ID NO: 98.
  • the polypeptide provided for herein comprising the formula of T-L1-Fc-L2-ECD-TM-ICD comprises an amino acid of SEQ ID NO: 98, wherein the VH of the target binding domain corresponds to amino acids 25-150 of SEQ ID NO: 98, the VL of the target binding domain corresponds to amino acids 172-283 of SEQ ID NO: 98, L1 comprises amino acids 284-301 of SEQ ID NO: 98, Fc comprises amino acids 302-542 of SEQ ID NO: 98, L2 is absent ECD comprises amino acids 543-584 of SEQ ID NO: 98, TM comprises amino acids 585-612 of SEQ ID NO: 98, and ICD comprises amino acids 613-634 of SEQ ID NO: 98, wherein the env incorporation motif comprises amino acids 627-634 of SEQ ID NO: 98.
  • the polypeptide provided for herein comprising the formula of T-L1-Fc-L2-ECD-TM-ICD, wherein T is a target binding domain, L1 is a polypeptide linker or -87- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT is absent, Fc is a variant Fc domain as provided for herein, L2 is a polypeptide linker or is absent, ECD is an extracellular domain, TM is a transmembrane domain, and ICD is an intracellular domain comprising a env incorporation motif, comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 98, wherein the target binding domain “T” of the polypeptide comprises an amino acid sequence SEQ ID NO: 39 and corresponds to amino acids 25-2
  • the polypeptide provided for herein comprising the formula of T-L1-Fc- L2-ECD-TM-ICD comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 98, wherein the target binding domain “T” of the polypeptide comprises an amino acid sequence SEQ ID NO: 39 and corresponds to amino acids 25-283 of SEQ ID NO: 98, L1 comprises an amino acid sequence of SEQ ID NO: 72 and corresponds to amino acids 284-301 of SEQ ID NO: 98, Fc comprises an amino acid sequence of SEQ ID NO: 104 and corresponds to amino acids 302-542 of SEQ ID NO: 98, L2 is absent, ECD comprises an amino acid sequence of SEQ ID NO: 60 and corresponds to amino acids 543-584 of SEQ ID NO: 98, TM comprises an amino acid sequence of SEQ ID NO: 62 and corresponds to amino acids 585- 612 of SEQ ID NO: 98, and ICD comprises amino acids 613-634 of SEQ ID NO: 98
  • the polypeptide provided for herein comprising the formula of T-L1-Fc-L2-ECD-TM-ICD comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 98, wherein the target binding domain “T” of the polypeptide comprises an amino acid sequence SEQ ID NO: 39 and corresponds to amino acids 25-283 of SEQ ID NO: 98, L1 comprises an amino acid sequence of SEQ ID NO: 72 and corresponds to amino acids 284-301 of SEQ ID NO: 98, Fc comprises an amino acid sequence of SEQ ID NO: 104 and corresponds to amino acids 302-542 of SEQ ID NO: 98, L2 is absent, ECD comprises an amino acid sequence of SEQ ID NO: 60 and corresponds to amino acids 543-584 of SEQ ID NO: 98, TM comprises an amino acid sequence -88- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT of SEQ ID NO: 62 and corresponds to amino acids 585
  • the polypeptide provided for herein comprising the formula of T-L1-Fc-L2-ECD-TM-ICD comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 98, wherein the target binding domain “T” of the polypeptide comprises an amino acid sequence SEQ ID NO: 39 and corresponds to amino acids 25-283 of SEQ ID NO: 98, L1 comprises an amino acid sequence of SEQ ID NO: 72 and corresponds to amino acids 284-301 of SEQ ID NO: 98, Fc comprises an amino acid sequence of SEQ ID NO: 104 and corresponds to amino acids 302-542 of SEQ ID NO: 98, L 2 is absent, ECD comprises an amino acid sequence of SEQ ID NO: 60 and corresponds to amino acids 543-584 of SEQ ID NO: 98, TM comprises an amino acid sequence of SEQ ID NO: 62 and corresponds to amino acids 585-612 of SEQ ID NO: 98, and ICD comprises amino acids 613- 634 of SEQ
  • the polypeptide provided for herein comprising the formula of T-L1-Fc- L2-ECD-TM-ICD comprises an amino acid sequence of SEQ ID NO: 98, wherein the target binding domain “T” of the polypeptide comprises an amino acid sequence SEQ ID NO: 39 and corresponds to amino acids 25-283 of SEQ ID NO: 98, L1 comprises an amino acid sequence of SEQ ID NO: 72 and corresponds to amino acids 284-301 of SEQ ID NO: 98, Fc comprises an amino acid sequence of SEQ ID NO: 104 and corresponds to amino acids 302-542 of SEQ ID NO: 98, L2 is absent, ECD comprises an amino acid sequence of SEQ ID NO: 60 and corresponds to amino acids 543-584 of SEQ ID NO: 98, TM comprises an amino acid sequence of SEQ ID NO: 62 and corresponds to amino acids 585-612 of SEQ ID NO: 98, and ICD comprises amino acids 613-634 of SEQ ID NO: 98, wherein the env
  • the polypeptide provided for herein comprising the formula of T-L1-Fc-L2-ECD-TM-ICD, wherein T is a target binding domain comprising a VH and a VL, L1 is a polypeptide linker or is absent, Fc is a variant Fc domain as provided for herein, L2 is a polypeptide linker or is absent, ECD is an extracellular domain, TM is a transmembrane domain, and ICD is an intracellular domain comprising a env incorporation motif, comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 98, wherein the VH of -89- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT the target binding domain comprises an amino acid sequence of SEQ ID NO: 36
  • the polypeptide provided for herein comprising the formula of T-L1-Fc-L2-ECD-TM-ICD comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 98, wherein the VH of the target binding domain comprises an amino acid sequence of SEQ ID NO: 36 and corresponds to amino acids 25-150 of SEQ ID NO: 98, the VL of the target binding domain comprises an amino acid sequence of SEQ ID NO: 37 and corresponds to amino acids 172-283 of SEQ ID NO: 98, L1 comprises an amino acid sequence of SEQ ID NO: 72 and corresponds to amino acids 284-301 of SEQ ID NO: 98, Fc comprises an amino acid sequence of SEQ ID NO: 104 and corresponds to amino acids 302-542 of SEQ ID NO: 98, L2 is absent, ECD comprises an amino acid sequence of SEQ ID NO: 60 and corresponds to amino acids 543-584 of SEQ ID NO: 98, TM comprises an amino acid sequence of SEQ ID NO:
  • the polypeptide provided for herein comprising the formula of T-L1-Fc- L2-ECD-TM-ICD comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 98, wherein the VH of the target binding domain comprises an amino acid sequence of SEQ ID NO: 36 and corresponds to amino acids 25-150 of SEQ ID NO: 98, the VL of the target binding domain comprises an amino acid sequence of SEQ ID NO: 37 and corresponds to amino acids 172-283 of SEQ ID NO: 98, L1 comprises an amino acid sequence of SEQ ID NO: 72 and corresponds to amino acids 284-301 of SEQ ID NO: 98, Fc comprises an amino acid sequence of SEQ ID NO: 104 and corresponds to amino acids 302-542 of SEQ ID NO: 98, L2 is absent, ECD comprises an amino acid sequence of SEQ ID NO: 60 and corresponds to amino acids 543-584 of SEQ ID NO: 98, TM comprises an amino acid sequence -90- IPTS
  • the polypeptide provided for herein comprising the formula of T-L1-Fc-L2-ECD-TM-ICD comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 98, wherein the VH of the target binding domain comprises an amino acid sequence of SEQ ID NO: 36 and corresponds to amino acids 25-150 of SEQ ID NO: 98, the VL of the target binding domain comprises an amino acid sequence of SEQ ID NO: 37 and corresponds to amino acids 172-283 of SEQ ID NO: 98, L1 comprises an amino acid sequence of SEQ ID NO: 72 and corresponds to amino acids 284-301 of SEQ ID NO: 98, Fc comprises an amino acid sequence of SEQ ID NO: 104 and corresponds to amino acids 302-542 of SEQ ID NO: 98, L2 is absent, ECD comprises an amino acid sequence of SEQ ID NO: 60 and corresponds to amino acids 543-584 of SEQ ID NO: 98, TM comprises an amino acid sequence of SEQ ID NO:
  • the polypeptide provided for herein comprising the formula of T-L1-Fc-L2-ECD-TM-ICD comprises an amino acid sequence of SEQ ID NO: 98, wherein the VH of the target binding domain comprises an amino acid sequence of SEQ ID NO: 36 and corresponds to amino acids 25-150 of SEQ ID NO: 98, the VL of the target binding domain comprises an amino acid sequence of SEQ ID NO: 37 and corresponds to amino acids 172-283 of SEQ ID NO: 98, L1 comprises an amino acid sequence of SEQ ID NO: 72 and corresponds to amino acids 284-301 of SEQ ID NO: 98, Fc comprises an amino acid sequence of SEQ ID NO: 104 and corresponds to amino acids 302-542 of SEQ ID NO: 98, L2 is absent, ECD comprises an amino acid sequence of SEQ ID NO: 60 and corresponds to amino acids 543-584 of SEQ ID NO: 98, TM comprises an amino acid sequence of SEQ ID NO: 62 and corresponds to amino acids 585-6
  • a VH peptide having a sequence as set forth in SEQ ID NO: 48 and a VL peptide having a sequence as set forth in SEQ ID NO: 49 are linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD.
  • the VH peptide having a sequence as set forth in SEQ ID NO: 48 and VL -91- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT peptide having a sequence as set forth in SEQ ID NO: 49 are linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD.
  • VH peptide having a sequence as set forth in SEQ ID NO: 48 and VL peptide having a sequence as set forth in SEQ ID NO: 49 are linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD.
  • VH peptide having a sequence as set forth in SEQ ID NO: 48 and VL peptide having a sequence as set forth in SEQ ID NO: 49 are linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD.
  • VH peptide having a sequence as set forth in SEQ ID NO: 48 and V L peptide having a sequence as set forth in SEQ ID NO: 49 are linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the VH peptide having a sequence as set forth in SEQ ID NO: 48 and VL peptide having a sequence as set forth in SEQ ID NO: 49 are linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the VH peptide having a sequence as set forth in SEQ ID NO: 48 and VL peptide having a sequence as set forth in SEQ ID NO: 49 are linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the VH peptide having a sequence as set forth in SEQ ID NO: 48 and VL peptide having a sequence as set forth in SEQ ID NO: 49 are linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the VH peptide having a sequence as set forth in SEQ ID NO: 48 and VL peptide having a sequence as set forth in SEQ ID NO: 49 linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD are anchored to the surface of a viral particle, such as those provided for herein.
  • the identities of L1, Fc, L2, ECD, TM, and ICD are as provided for herein.
  • the VH and VL peptides bind to an immune cell, such as those provided herein.
  • the VH peptide comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 48; and the VL peptide comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to -92- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT a sequence of SEQ ID NO: 49 are linked to a stalk portion (S1) comprising an Fc region as provided for herein.
  • the Fc region further comprising a transmembrane domain has a formula of L1-Fc-L2-X1, wherein L1 is a linker as provided for herein or is absent, Fc is a variant Fc region as provided for herein, L2 is a linker as provided for herein or is absent, and X1 is a polypeptide comprising a transmembrane domain as provided for herein.
  • X1 may comprises a polypeptide having the formula ECD-TM-ICD, wherein ECD is an extracellular domain, or a fragment thereof as provided for herein or is absent, TM is a transmembrane domain as provided for herein, and ICD is an intracellular domain as provided for herein or is absent.
  • the VH peptide comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 48; and the VL peptide comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 49 linked to a stalk portion (S1) comprising an Fc region (L1-Fc- L2-X1) comprising an ECD, a TM, and an ICD are anchored to the surface of a viral particle, -94- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT such as those provided for herein.
  • VH and VL peptides bind to an immune cell, such as those provided herein.
  • a polypeptide comprising a VH peptide and a VL peptide, wherein the VH peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 48; and the VL peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 49.
  • the polypeptide comprises a V H peptide and a V L peptide, wherein the VH peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 48; and the VL peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 49; provided that the VH peptide and a VL peptide comprises a light chain CDR having a sequence of SEQ ID NO: 45-47; and/or a heavy chain CDR having a sequence of SEQ ID NO: 42-44.
  • the polypeptide comprises a VH peptide and a VL peptide, wherein the VH peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 48; and the VL peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 49; provided that the VH peptide and a VL peptide comprise a light chain CDR1 having a sequence of SEQ ID NO: 45; a light chain CDR2 having a sequence of SEQ ID NO: 46; a light chain CDR3 having a sequence of SEQ ID NO: 47; and/or a heavy chain CDR1
  • the CDRs in the VH or VL chain are as set forth in the combinations provided for herein.
  • the polypeptide comprises a VH peptide and a VL peptide, wherein the VH peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 48; and the VL peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 49; provided that the VL peptide comprises a LCDR1 having a sequence of SEQ ID NO: 45; a LCDR2 having a sequence of SEQ ID NO: 46; and a LCDR3 having a sequence of SEQ ID NO:
  • the polypeptide comprises a VH peptide and a VL peptide, wherein the VH peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 48; and the VL peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 49; provided that the VL peptide comprises a LCDR1 having a sequence of SEQ ID NO: 45, wherein the LCDR1 comprises at most 1 conservative amino acid substitution, a LCDR2 having a sequence of SEQ ID NO: 46, wherein the LCDR2 comprises at most 1 conservative amino acid substitution, and a LCDR3 having a sequence of
  • the polypeptide comprises a VH peptide and a VL peptide, wherein the VH peptide comprises a sequence of SEQ ID NO: 48 and the VL peptide comprises a sequence of SEQ ID NO: 49.
  • the polypeptide as provided herein binds to non-human primate CD8.
  • the polypeptide as provided herein binds to human CD8.
  • the different polypeptides (VH or VL) described herein can be linked with a peptide linker or not linked with a peptide linker and instead for a continuous sequence.
  • the peptide linker comprises a sequence of (GGGGS)n (SEQ ID NO: 55), wherein each n is independently 1-5. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5.
  • the linked peptide format can be represented by a formula of VH-Z-VL or VL-Z-VH, wherein Z is the peptide linker. In some embodiments, Z is (GGGGS)n (SEQ ID NO: 55), wherein each n is independently 1-5. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3.
  • n is 4. In some embodiments, n is 5. -96- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT
  • the polypeptide comprising the linked peptide represented by a formula of VL-Z-VH comprises a heavy chain variable region as set forth in SEQ ID NO: 48 linked via a linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 72) to a light chain variable region as set forth in SEQ ID NO: 49.
  • the polypeptide comprising a VL linked via a peptide linker to a VH has the sequence as set forth below, NIVLTQSPASLAVSLGQRATISCRASESVDGFGNSFMNWYQQKPGQSPKLLIY LASNLESGVPARFSGSGSRTDFTLTIDPVEADDAATYYCQQNNEDPYTFGGGT KLEIKRGGGGSGGGGSGGGGSGGGGSEVQLQQSGPELVKPGASVKISCKASR YTFTDYNLHWVKLSHEKSLEWIGFIYPYNGGTGYNQKFKNKAKLTVDYSSST AYMELRSLTSVDAAVYYCARDHRYNEGVSFDYWGQGTTLTVSS (SEQ ID NO: 50).
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 50.
  • the polypeptide comprises a sequence that is at least 90% identical to a sequence of SEQ ID NO: 50.
  • the polypeptide comprises a sequence that is at least 95% identical to a sequence of SEQ ID NO: 50.
  • the polypeptide comprises a sequence that is at least 99% identical to a sequence of SEQ ID NO: 50.
  • the polypeptide comprises a sequence as set forth in SEQ ID NO: 50.
  • the polypeptide as set forth in SEQ ID NO: 50 is an antibody, or an antigen binding fragment thereof.
  • the antibody is an anti-CD8 antibody.
  • the anti-CD8 antibody binds to non- human primate CD8.
  • the anti-CD8 antibody binds to human CD8.
  • the polypeptide comprising the linked peptide represented by a formula of VH-Z-VL comprises a light chain variable region as set forth in SEQ ID NO: 49 linked via a linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 72) to a heavy chain variable region as set forth in SEQ ID NO: 48.
  • the polypeptide comprising a VH linked via a peptide linker to a VL has the sequence as set forth below, EVQLQQSGPELVKPGASVKISCKASRYTFTDYNLHWVKLSHEKSLEWIGFIYP YNGGTGYNQKFKNKAKLTVDYSSSTAYMELRSLTSVDAAVYYCARDHRYN EGVSFDYWGQGTTLTVSSGGGGSGGGGSGGGGSGGGGSNIVLTQSPASLAVS LGQRATISCRASESVDGFGNSFMNWYQQKPGQSPKLLIYLASNLESGVPARFS GSGSRTDFTLTIDPVEADDAATYYCQQNNEDPYTFGGGTKLEIKR (SEQ ID NO: 51).
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 51. In some embodiments, the polypeptide comprises a sequence that is at least 90% identical to a sequence of SEQ ID NO: 51. In some embodiments, the polypeptide comprises a sequence that is at least 95% identical to a sequence of SEQ ID NO: 51.
  • the polypeptide comprises a sequence that is at least 99% identical to a sequence of SEQ ID NO: 51. In some embodiments, the polypeptide comprises a sequence as set forth in SEQ ID NO: 51. In some embodiments, the polypeptide as set forth in SEQ ID NO: 51 is an antibody, or an antigen binding fragment thereof. In some embodiments, the antibody is an anti-CD8 antibody. In some embodiments, the anti-CD8 antibody binds to non- human primate CD8. In some embodiments, the anti-CD8 antibody binds to human CD8.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 50 and comprises a stalk portion (S1) comprising an Fc region, such as those provided herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 50 and comprises a stalk portion (S1) comprising an Fc region, said Fc region further comprising a transmembrane domain, such as those provided herein.
  • the Fc region further comprising a transmembrane domain has a formula of L1-Fc-L2-X1, wherein L1 is a linker as provided for herein or is absent, Fc is a variant Fc region as provided for herein, L2 is a linker as provided for herein or is absent, and X1 is a polypeptide comprising a transmembrane domain as provided for herein.
  • X1 may comprises a polypeptide having the formula ECD-TM-ICD, wherein ECD is an extracellular domain, or a fragment thereof as provided for herein or is absent, TM is a transmembrane domain as provided for herein, and ICD is an intracellular domain as provided for herein or is absent.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 50 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD.
  • SEQ ID NO: 50 comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 50 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, -98- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 50 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 50 and comprises a stalk portion (S1) comprising an Fc region (L1- Fc-L2-X1) comprising a CD8 and/or CD
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 50 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a T M , and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 50 and comprises a stalk portion (S1) comprising an Fc region (L1- Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 50 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 50 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 50 and comprising a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD, is anchored to the surface of a viral particle, such as those provided for herein .
  • the identities of L1, Fc, L2, ECD, TM, and ICD are as provided for herein.
  • the polypeptide bind to an immune cell, such as those provided herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 51 and comprises a stalk portion (S1) comprising an Fc region, such -99- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT as those provided herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 51 and comprises a stalk portion (S1) comprising an Fc region, said Fc region further comprising a transmembrane domain, such as those provided herein.
  • the Fc region further comprising a transmembrane domain has a formula of L1-Fc-L2-X1, wherein L1 is a linker as provided for herein or is absent, Fc is a variant Fc region as provided for herein, L2 is a linker as provided for herein or is absent, and X1 is a polypeptide comprising a transmembrane domain as provided for herein.
  • X1 may comprises a polypeptide having the formula ECD-TM-ICD, wherein ECD is an extracellular domain, or a fragment thereof as provided for herein or is absent, TM is a transmembrane domain as provided for herein, and ICD is an intracellular domain as provided for herein or is absent.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 51 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 51 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 51 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 51 and comprises a stalk portion (S1) comprising an Fc region (L1- Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 51 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 51 and comprises a stalk portion (S1) comprising an Fc region (L1- Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD, wherein the ICD comprises -100- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT an env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 51 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 51 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 51 and comprising a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD, is anchored to the surface of a viral particle, such as those provided for herein .
  • the identities of L1, Fc, L2, ECD, TM, and ICD are as provided for herein.
  • the polypeptide bind to an immune cell, such as those provided herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 50 and comprises a stalk portion (S1) comprising an Fc region, such as those provided herein. In some embodiments, the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 50 and comprises a stalk portion (S1) comprising an Fc region, said Fc region further comprising a transmembrane domain, such as those provided herein.
  • the Fc region further comprising a transmembrane domain has a formula of L1-Fc-L2-X1, wherein L1 is a linker as provided for herein or is absent, Fc is a variant Fc region as provided for herein, L2 is a linker as provided for herein or is absent, and X1 is a polypeptide comprising a transmembrane domain as provided for herein.
  • X1 may comprises a polypeptide having the formula ECD-TM-ICD, wherein ECD is an extracellular domain, or a fragment thereof as provided for herein or is absent, TM is a transmembrane domain as provided for herein, and ICD is an intracellular domain as provided for herein or is absent.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 50 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 50 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or -101- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT CD28 ECD, a TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 50 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 50 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 50 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 50 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 50 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 50 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprising a sequence having a sequence as set forth in SEQ ID NO: 50 and comprising a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD, is anchored to the surface of a viral particle, such as those provided for herein .
  • the identities of L1, Fc, L2, ECD, TM, and ICD are as provided for herein.
  • the polypeptide bind to an immune cell, such as those provided herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 51 and comprises a stalk portion (S1) comprising an Fc region, such as those provided herein. In some embodiments, the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 51 and comprises a stalk portion (S1) comprising an Fc region, said Fc region further comprising a transmembrane domain, such as those provided herein.
  • the Fc region further comprising a transmembrane domain has a formula of L1-Fc-L2-X1, wherein L1 is a linker as provided for herein or is absent, Fc is a variant Fc region as provided for herein, L2 is a linker as provided for herein or is absent, and X1 is a polypeptide comprising a transmembrane domain as provided for herein.
  • X1 may comprises a polypeptide having the formula ECD-TM-ICD, wherein ECD is an extracellular domain, or a fragment thereof as provided for herein or is absent, TM is a transmembrane domain as provided for herein, and ICD is an intracellular domain as provided for herein or is absent.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 51 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 51 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 51 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 51 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 51 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 51 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 51 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 51 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an env incorporation motif as provided for herein.
  • the polypeptide comprising a sequence having a sequence as set forth in SEQ ID NO: 51 and comprising a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising an ECD, a TM, and an ICD, is anchored to the surface of a viral particle, such as those provided for herein .
  • the identities of L1, Fc, L2, ECD, TM, and ICD are as provided for herein.
  • the polypeptide bind to an immune cell, such as those provided herein.
  • the VH and VL polypeptides are linked to a stalk portion (S1) comprising a flexible polypeptide (L3) as provided for herein. In some embodiments, the VH and VL polypeptides are linked to a stalk portion (S1) comprising a flexible polypeptide further comprising a polypeptide comprising a transmembrane domain as provided for herein.
  • the flexible polypeptide further comprising a polypeptide comprising a transmembrane domain is represented by the formula L3-X1, wherein L3 is a flexible polypeptide as provided for herein and X1 is as provided for herein.
  • X1 may comprise a polypeptide having the formula of ECD-TM-ICD, wherein ECD is an extracellular domain, or a fragment thereof as provided for herein or is absent, T M is a transmembrane domain as provided for herein, and ICD is an intracellular domain as provided for herein or is absent.
  • ECD include, but are not limited to, a CD8 and/or CD28 ECD as provided for herein.
  • TM examples include, but are not limited to, a CD8 and/or CD28 transmembrane domain as provided for herein.
  • ECD the ICD
  • the ECD, the ICD, or both may be optionally absent.
  • X1 comprises a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD comprising an Env incorporation motif
  • X1 members i) a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD comprising an Env incorporation motif; ii) a CD8 and/or CD28 TM, and an ICD comprising an Env incorporation motif wherein the ECD is absent; iii) a CD8 and/or CD28 ECD, and a CD8 and/or CD28 TM, wherein the ICD is absent; and iv) a CD8 and/or CD28 TM wherein both the
  • X1 comprises a CD8 and/or CD28 TM and an ICD comprising an Env incorporation motif is understood to encompass the following X1 members: i) a CD8 and/or CD28 TM and an ICD comprising an Env incorporation motif; and ii) a CD8 and/or CD28 TM wherein the ICD is absent.
  • X1 comprises a CD8 and/or CD28 ECD and a CD8 and/or CD28 TM is understood to encompass the following X1 members: i) a CD8 and/or CD28 ECD and a CD8 and/or CD28 TM; and ii) a CD8 and/or CD28 TM wherein the ECD is absent.
  • X1 comprises an ECD, a CD8 and/or CD28 TM, and an ICD
  • X1 members i) an ECD, a CD8 and/or CD28 TM, and an ICD; ii) an ECD, and a CD8 and/or CD28 TM wherein the ICD is absent; iii) a CD8 and/or CD28 TM, and an ICD wherein the ECD is absent; and iv) a CD8 and/or CD28 TM wherein the ECD and the ICD are absent.
  • an embodiment wherein -104- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT X1 comprises a CD8 and/or CD28 TM and an ICD is understood to encompass the following X1 members: i) a CD8 and/or CD28 TM and an ICD; and ii) a CD8 and/or CD28 TM wherein the ICD is absent.
  • X1 comprises an ECD and a CD8 and/or CD28 TM is understood to encompass the following X1 members: i) an ECD and a CD8 and/or CD28 TM; and ii) a CD8 and/or CD28 TM wherein the ECD is absent.
  • X1 comprises a CD8 and/or CD28 ECD, a TM, and an ICD.
  • X1 comprises an ECD, a CD8 and/or CD28 TM, and an ICD.
  • X1 comprises a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD.
  • X 1 comprises an ECD, a T M , and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • X1 comprises a CD8 and/or CD28 ECD, a TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • X1 comprises an ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • X1 comprises a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the VH and VL polypeptides provided herein are linked to a stalk portion (S1) comprising a flexible polypeptide (L3) as provided for herein. In some embodiments, the VH and VL polypeptides provided herein are linked to a stalk portion (S1) comprising a flexible polypeptide (L3) further comprising a polypeptide comprising a transmembrane domain as provided for herein. In some embodiments the flexible polypeptide (L3) further comprising a polypeptide comprising a transmembrane domain is represented by the formula L3-X1, wherein L3 is a flexible polypeptide as provided for herein and X1 is a polypeptide comprising a transmembrane domain as provided for herein.
  • X1 may comprise a polypeptide having the formula of ECD-TM-ICD, wherein ECD is an extracellular domain, or a fragment thereof as provided for herein, or is absent; TM is a transmembrane domain as provided for herein; and ICD is an intracellular domain as provided for herein.
  • the VH and VL polypeptides provided herein are linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD.
  • the VH and VL polypeptides provided herein are linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD.
  • the VH and VL polypeptides provided herein are linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD.
  • the VH and VL polypeptides provided herein are linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the VH and VL polypeptides provided herein are linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the VH and VL polypeptides provided herein are linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the V H and V L polypeptides provided herein are linked to a stalk portion (S 1 ) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the VH and VL polypeptides provided herein linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a TM, and an ICD are anchored to the surface of a viral particle, such as those provided for herein.
  • the identities of L3, X1, ECD, TM, and ICD are as provided for herein.
  • the VH and VL polypeptides bind to an immune cell, such as those provided herein.
  • a VH peptide having a sequence as set forth in SEQ ID NO: 36 and a VL peptide having a sequence as set forth in SEQ ID NO: 37 are linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a TM, and an ICD.
  • the VH peptide having a sequence as set forth in SEQ ID NO: 36 and VL peptide having a sequence as set forth in SEQ ID NO: 37 are linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD.
  • the VH peptide having a sequence as set forth in SEQ ID NO: 36 and VL peptide having a sequence as set forth in SEQ ID NO: 37 are linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD.
  • the VH peptide having a sequence as set forth in SEQ ID NO: 36 and VL peptide having a sequence as set forth in SEQ ID NO: 37 are linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD.
  • VH peptide having a sequence as set forth in SEQ ID NO: 36 and VL peptide having a sequence as set forth in SEQ ID NO: 37 are linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the VH peptide having a sequence as set forth in SEQ ID -106- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT NO: 36 and VL peptide having a sequence as set forth in SEQ ID NO: 37 are linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the VH peptide having a sequence as set forth in SEQ ID NO: 36 and VL peptide having a sequence as set forth in SEQ ID NO: 37 are linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the VH peptide having a sequence as set forth in SEQ ID NO: 36 and VL peptide having a sequence as set forth in SEQ ID NO: 37 are linked to a stalk portion (S1) comprising a flexible polypeptide (L 3 -X 1 ) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the VH peptide having a sequence as set forth in SEQ ID NO: 36 and VL peptide having a sequence as set forth in SEQ ID NO: 37 linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a TM, and an ICD are anchored to the surface of a viral particle, such as those provided for herein.
  • the identities of L3, X1, ECD, TM, and ICD are as provided for herein.
  • the VH and VL peptides bind to an immune cell, such as those provided herein.
  • the flexible polypeptide further comprising a polypeptide comprising a transmembrane domain is represented by the formula L3-X1, wherein L3 is a flexible polypeptide as provided for herein and X1 is a polypeptide comprising a transmembrane domain as provided for herein.
  • X1 may comprise a polypeptide having the formula of ECD-TM-ICD, wherein ECD is an extracellular domain, or fragment thereof as provided for herein, or is absent; TM is a -107- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT transmembrane domain as provided for herein; and ICD is an intracellular domain as provided for herein, or is absent.
  • the VH peptide comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 36; and the VL peptide comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 37 linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a TM, and an ICD are anchored to the surface of a viral particle, such as those provided for herein.
  • the identities of L3, X1, ECD, TM, and ICD are as provided for herein.
  • the VH and VL peptides bind to an immune cell, such as those provided herein.
  • a polypeptide is provided comprising a VH peptide and a VL peptide, wherein the VH peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 36; and the VL peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 37.
  • the polypeptide comprises a VH peptide and a VL peptide, wherein the VH peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 36; and the VL peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 37; provided that the VH peptide and a VL peptide comprises a light chain CDR having a sequence of SEQ ID NO: 33-35; and/or a heavy chain CDR having a sequence of SEQ ID NO: 30-32.
  • the polypeptide comprises a VH peptide and a VL peptide, -109- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT wherein the VH peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 36; and the VL peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 37; provided that the VH peptide and a VL peptide comprise a light chain CDR1 having a sequence of SEQ ID NO: 33; a light chain CDR2 having a sequence of SEQ ID NO: 34; a light chain
  • the CDRs in the V H or V L chain are as set forth in the combinations provided for herein.
  • the polypeptide comprises a VH peptide and a VL peptide, wherein the VH peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 36; and the VL peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 37; provided that the VL peptide comprises a LCDR1 having a sequence of SEQ ID NO: 33; a LCDR2 having a sequence of SEQ ID NO: 34; and a LCDR3 having a sequence of S
  • the polypeptide comprises a VH peptide and a VL peptide, wherein the VH peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 36; and the VL peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 37; provided that the VL peptide comprises a LCDR1 having a sequence of SEQ ID NO: 33, wherein the LCDR1 comprises at most 1 conservative amino acid substitution, a LCDR2 having a sequence of SEQ ID NO: 34, wherein the LCDR2 comprises at most 1 conservative amino acid substitution, and a LCDR3 having a sequence of
  • the polypeptide comprises a VH peptide and a VL peptide, wherein the VH peptide comprises a sequence of SEQ ID NO: 36 and the VL peptide comprises a sequence of SEQ ID NO: 37.
  • the polypeptide as provided herein binds to non-human primate CD7.
  • the polypeptide as provided herein binds to human CD7.
  • the different polypeptides (VH or VL) described herein can be linked with a peptide linker or not linked with a peptide linker and instead for a continuous sequence.
  • the peptide linker comprises a sequence of (GGGGS) n (SEQ ID NO: 55), wherein each n is independently 1-5. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5.
  • the linked peptide format can be represented by a formula of VH-Z-VL or VL-Z-VH, wherein Z is the peptide linker. In some embodiments, Z is (GGGGS)n (SEQ ID NO: 55), wherein each n is independently 1-5. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3.
  • n is 4. In some embodiments, n is 5. In some embodiments, the polypeptide comprising the linked peptide represented by a formula of VL-Z-VH comprises a heavy chain variable region as set forth in SEQ ID NO: 36 linked via a linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 72) to a light chain variable region as set forth in SEQ ID NO: 37.
  • the polypeptide comprising a VL linked via a peptide linker to a VH has the sequence as set forth below, DILLTQSPAILSVSPGERVSFSCRASQSIGTSIHWYQQRTNDSPRLLIKYASESIS GIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQSNSWPTTFGGGTKLEIKRGG GGSGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKLSCKASGYPFTSYW IHWVKQRPGRGLEWLGRIDPNSGDTKYNEKFKNKATLTVDKSSTTAYMQLS SLTSEDSAVYYCARSPYYSNDNSMDYWGQGTSVTVSS (SEQ ID NO: 38).
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 38.
  • the polypeptide comprises a sequence that is at least 90% identical to a sequence of SEQ ID NO: 38.
  • the polypeptide comprises a sequence that is at least 95% identical to a sequence of SEQ ID NO: 38.
  • the polypeptide comprises a sequence that is at least 99% identical to a sequence of SEQ ID NO: 38.
  • the polypeptide comprises a sequence -111- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT as set forth in SEQ ID NO: 38.
  • the polypeptide as set forth in SEQ ID NO: 38 is an antibody, or an antigen binding fragment thereof.
  • the antibody is an anti-CD7 antibody.
  • the anti-CD7 antibody binds to non- human primate CD7.
  • the anti-CD7 antibody binds to human CD7.
  • the polypeptide comprising the linked peptide represented by a formula of VH-Z-VL comprises a light chain variable region as set forth in SEQ ID NO: 37 linked via a linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 72) to a heavy chain variable region as set forth in SEQ ID NO: 36.
  • a polypeptide comprising a VH linked via a peptide linker to a VL has the sequence as set forth below, QVQLQQPGAELVKPGASVKLSCKASGYPFTSYWIHWVKQRPGRGLEWLGRI DPNSGDTKYNEKFKNKATLTVDKSSTTAYMQLSSLTSEDSAVYYCARSPYYS NDNSMDYWGQGTSVTVSSGGGGSGGGGSGGGGSGGGGSDILLTQSPAILSVS PGERVSFSCRASQSIGTSIHWYQQRTNDSPRLLIKYASESISGIPSRFSGSGSGT DFTLSINSVESEDIADYYCQQSNSWPTTFGGGTKLEIKR (SEQ ID NO: 39).
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 39.
  • the polypeptide comprises a sequence that is at least 90% identical to a sequence of SEQ ID NO: 39.
  • the polypeptide comprises a sequence that is at least 95% identical to a sequence of SEQ ID NO: 39.
  • the polypeptide comprises a sequence that is at least 99% identical to a sequence of SEQ ID NO: 39.
  • the polypeptide comprises a sequence as set forth in SEQ ID NO: 39.
  • the polypeptide as set forth in SEQ ID NO: 39 is an antibody, or an antigen binding fragment thereof.
  • the antibody is an anti-CD7 antibody.
  • the anti-CD7 antibody binds to non- human primate CD7.
  • the anti-CD7 antibody binds to human CD7.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 38 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3) as provided for herein.
  • a polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 38 and comprises a stalk portion (S1) comprising a flexible polypeptide further comprising a polypeptide comprising a transmembrane domain as provided for herein.
  • the flexible polypeptide further comprising a polypeptide comprising a transmembrane domain is represented by the -112- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT formula L3-X1, wherein L3 is a flexible polypeptide as provided for herein and X1 is a polypeptide comprising a transmembrane domain as provided for herein.
  • X1 may comprise a polypeptide having the formula of ECD-TM-ICD, wherein ECD is an extracellular domain, or fragment thereof as provided for herein, or is absent; TM is a transmembrane domain as provided for herein; and ICD is an intracellular domain as provided for herein or is absent.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 38 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 38 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 38 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 38 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 38 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 38 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 38 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, -113- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 38 and comprising a stalk portion (S1) comprising a flexible polypeptide (L3- X1) comprising an ECD, a TM, and an ICD, is anchored to the surface of a viral particle, such as those provided for herein .
  • the identities of L3, ECD, TM, and ICD are as provided for herein.
  • thepolypeptide bind to an immune cell, such as those provided herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 39 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3) as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 39 and comprises a stalk portion (S1) comprising a flexible polypeptide further comprising a polypeptide comprising a transmembrane domain as provided for herein.
  • the flexible polypeptide further comprising a polypeptide comprising a transmembrane domain is represented by the formula L3-X1, wherein L3 is a flexible polypeptide as provided for herein and X1 is a polypeptide comprising a transmembrane domain as provided for herein.
  • X1 may comprise a polypeptide having the formula of ECD-TM-ICD, wherein ECD is an extracellular domain, or fragment thereof as provided for herein, or is absent; TM is a transmembrane domain as provided for herein; and ICD is an intracellular domain as provided for herein, or is absent.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 39 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 39 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 39 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD.
  • the -114- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 39 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 39 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 39 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 39 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 39 and comprising a stalk portion (S1) comprising a flexible polypeptide (L3- X1) comprising an ECD, a TM, and an ICD, is anchored to the surface of a viral particle, such as those provided for herein .
  • the identities of L3, ECD, TM, and ICD are as provided for herein.
  • thepolypeptide bind to an immune cell, such as those provided herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 38 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3) as provided for herein. In some embodiments, the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 38 and comprises a stalk portion (S1) comprising a flexible polypeptide further comprising a polypeptide comprising a transmembrane domain as provided for herein.
  • the flexible polypeptide further comprising a polypeptide comprising a transmembrane domain is represented by the formula L3-X1, wherein L3 is a flexible polypeptide as provided for herein and X1 is a polypeptide comprising a transmembrane domain as provided for herein.
  • X1 may comprise a -115- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT polypeptide having the formula of ECD-TM-ICD, wherein ECD is an extracellular domain, or fragment thereof as provided for herein, or is absent; TM is a transmembrane domain as provided for herein; and ICD is an intracellular domain as provided for herein or is absent.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 38 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 38 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 38 and comprises a stalk portion (S 1 ) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 38 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 38 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 38 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 38 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprising a sequence having a sequence as set forth in SEQ ID NO: 38 and comprising a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a TM, and an ICD is anchored to the surface of a viral particle, such as those provided for herein .
  • the identities of L3, ECD, TM, and ICD are as provided for herein.
  • the polypeptide bind to an immune cell, such as those provided herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 39 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3) as provided for herein.
  • a polypeptide comprises a sequence having -116- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT a sequence as set forth in SEQ ID NO: 39 and comprises a stalk portion (S1) comprising a flexible polypeptide further comprising a polypeptide comprising a transmembrane domain as provided for herein.
  • the flexible polypeptide further comprising a polypeptide comprising a transmembrane domain is represented by the formula L3-X1, wherein L3 is a flexible polypeptide as provided for herein and X1 is a polypeptide comprising a transmembrane domain as provided for herein.
  • X1 may comprise a polypeptide having the formula of ECD-TM-ICD, wherein ECD is an extracellular domain or fragment thereof as provided for herein, or is absent; TM is a transmembrane domain as provided for herein; and ICD is an intracellular domain as provided for herein, or is absent.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 39 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 39 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 39 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 39 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 39 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 39 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 39 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprising a sequence having a sequence as set forth in SEQ ID NO: 39 and comprising a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a TM, and an ICD, is anchored to the surface of a -117- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT viral particle, such as those provided for herein .
  • the identities of L3, ECD, TM, and ICD are as provided for herein.
  • the polypeptide bind to an immune cell, such as those provided herein.
  • a VH peptide having a sequence as set forth in SEQ ID NO: 48 and a VL peptide having a sequence as set forth in SEQ ID NO: 49 are linked to a stalk portion (S1) comprising a flexible polypeptide (L3) as provided for herein.
  • the VH peptide having a sequence as set forth in SEQ ID NO: 48 and the VL peptide having a sequence as set forth in SEQ ID NO: 49 are linked to a stalk portion (S1) comprising a flexible polypeptide further comprising a polypeptide comprising a transmembrane domain as provided for herein.
  • the flexible polypeptide further comprising a polypeptide comprising a transmembrane domain is represented by the formula L3-X1, wherein L3 is a flexible polypeptide as provided for herein and X1 is a polypeptide comprising a transmembrane domain as provided for herein.
  • X1 may comprise a polypeptide having the formula of ECD-TM-ICD, wherein ECD is an extracellular domain or fragment thereof as provided for herein, or is absent; TM is a transmembrane domain as provided for herein; and ICD is an intracellular domain as provided for herein, or is absent.
  • the VH peptide having a sequence as set forth in SEQ ID NO: 48 and the VL peptide having a sequence as set forth in SEQ ID NO: 49 are linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD.
  • the VH peptide having a sequence as set forth in SEQ ID NO: 48 and VL peptide having a sequence as set forth in SEQ ID NO: 49 are linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD.
  • VH peptide having a sequence as set forth in SEQ ID NO: 48 and VL peptide having a sequence as set forth in SEQ ID NO: 49 are linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD.
  • S1 a stalk portion comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD.
  • VH peptide having a sequence as set forth in SEQ ID NO: 48 and VL peptide having a sequence as set forth in SEQ ID NO: 49 are linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • VH peptide having a sequence as set forth in SEQ ID NO: 48 and VL peptide having a sequence as set forth in SEQ ID NO: 49 are linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the VH peptide -118- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT having a sequence as set forth in SEQ ID NO: 48 and VL peptide having a sequence as set forth in SEQ ID NO: 49 are linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the VH peptide having a sequence as set forth in SEQ ID NO: 48 and VL peptide having a sequence as set forth in SEQ ID NO: 49 are linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the VH peptide having a sequence as set forth in SEQ ID NO: 48 and VL peptide having a sequence as set forth in SEQ ID NO: 49 linked to a stalk portion (S 1 ) comprising a flexible polypeptide (L 3 - X1) comprising an ECD, a TM, and an ICD are anchored to the surface of a viral particle, such as those provided for herein.
  • the identities of L3, X1, ECD, TM, and ICD are as provided for herein.
  • the VH and VL peptides bind to an immune cell, such as those provided herein.
  • the flexible polypeptide further comprising a polypeptide comprising a transmembrane domain is represented by the formula L3-X1, wherein L3 is a flexible polypeptide as provided for herein and X1 is a polypeptide comprising a transmembrane domain as provided for herein.
  • X1 may comprise a polypeptide having the formula of ECD-TM-ICD, wherein ECD is an extracellular domain, or fragment thereof as provided for herein, or is absent; TM is a transmembrane domain as provided for herein; and ICD is an intracellular domain as provided for herein or is absent.
  • the VH peptide comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 48; and the VL peptide comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 49 linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a TM, and an ICD are anchored to the surface of a viral particle, such as those provided for herein.
  • the identities of L3, X1, ECD, TM, and ICD are as provided for herein.
  • the VH and VL peptides bind to an immune cell, such as those provided herein.
  • a polypeptide is provided comprising a VH peptide and a VL peptide, wherein the VH peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 48; and the VL peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 49.
  • the polypeptide comprises a VH peptide and a VL peptide, wherein the VH peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 48; and the VL peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 49; provided that the VH peptide and a VL peptide comprise a light chain CDR having a sequence of SEQ ID NO: 45-47; and/or a heavy chain CDR having a sequence of SEQ ID NO: 42-44.
  • the polypeptide comprises a VH peptide and a VL peptide, wherein the VH peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 48; and the VL peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, -121- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 49; provided that the VH peptide and a VL peptide comprise a light chain CDR1 having a sequence of SEQ ID NO: 45; a light chain CDR2 having a sequence of SEQ ID NO: 46; a light chain
  • the CDRs in the VH or VL chain are as set forth in the combinations provided for herein.
  • the polypeptide comprises a VH peptide and a VL peptide, wherein the VH peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 48; and the VL peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 49; provided that the VL peptide comprises a LCDR1 having a sequence of SEQ ID NO: 45; a LCDR2 having a sequence of SEQ ID NO: 46; and a LCDR3 having a sequence of SEQ ID NO:
  • the polypeptide comprises a VH peptide and a VL peptide, wherein the VH peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 48; and the VL peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 49; provided that the VL peptide comprises a LCDR1 having a sequence of SEQ ID NO: 45, wherein the LCDR1 comprises at most 1 conservative amino acid substitution, a LCDR2 having a sequence of SEQ ID NO: 46, wherein the LCDR2 comprises at most 1 conservative amino acid substitution, and a LCDR3 having a sequence of
  • the polypeptide comprises a VH peptide and a VL peptide, wherein the VH peptide comprises a sequence of SEQ ID NO: 48 and the VL peptide comprises a sequence of SEQ ID NO: 49.
  • the polypeptide as provided herein binds to non-human primate CD8.
  • a polypeptide as provided herein binds to human CD8.
  • the different polypeptides (VH or VL) described herein can be linked with a peptide linker or not linked with a peptide linker and instead for a continuous sequence.
  • the peptide linker comprises a sequence of (GGGGS)n (SEQ ID NO: 55), wherein each n is independently 1-5. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5.
  • the linked peptide format can be represented by a formula of VH-Z-VL or VL-Z-VH, wherein Z is the peptide linker. In some embodiments, Z is (GGGGS)n (SEQ ID NO: 55), wherein each n is independently 1-5. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3.
  • n is 4. In some embodiments, n is 5. In some embodiments, the polypeptide comprising the linked peptide represented by a formula of VL-Z-VH comprises a heavy chain variable region as set forth in SEQ ID NO: 48 linked via a linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 72) to a light chain variable region as set forth in SEQ ID NO: 49.
  • the polypeptide comprising a VL linked via a peptide linker to a VH has the sequence as set forth below, NIVLTQSPASLAVSLGQRATISCRASESVDGFGNSFMNWYQQKPGQSPKLLIY LASNLESGVPARFSGSGSRTDFTLTIDPVEADDAATYYCQQNNEDPYTFGGGT KLEIKRGGGGSGGGGSGGGGSGGGGSEVQLQQSGPELVKPGASVKISCKASR YTFTDYNLHWVKLSHEKSLEWIGFIYPYNGGTGYNQKFKNKAKLTVDYSSST AYMELRSLTSVDAAVYYCARDHRYNEGVSFDYWGQGTTLTVSS (SEQ ID NO: 50).
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 50.
  • the polypeptide comprises a sequence that is at least 90% identical to a sequence of SEQ ID NO: 50.
  • the polypeptide comprises a sequence that is at least 95% identical to a sequence of SEQ ID NO: 50.
  • the polypeptide comprises a sequence that is at least 99% identical to a sequence of SEQ ID NO: 50.
  • the polypeptide comprises a sequence as set forth in SEQ ID NO: 50.
  • the polypeptide as set forth in SEQ ID -123- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT NO: 50 is an antibody, or an antigen binding fragment thereof.
  • the antibody is an anti-CD8 antibody.
  • the anti-CD8 antibody binds to non- human primate CD8.
  • the anti-CD8 antibody binds to human CD8.
  • the polypeptide comprising the linked peptide represented by a formula of VH-Z-VL comprises a light chain variable region as set forth in SEQ ID NO: 49 linked via a linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 72) to a heavy chain variable region as set forth in SEQ ID NO: 48.
  • the polypeptide comprising a VH linked via a peptide linker to a VL has the sequence as set forth below, EVQLQQSGPELVKPGASVKISCKASRYTFTDYNLHWVKLSHEKSLEWIGFIYP YNGGTGYNQKFKNKAKLTVDYSSSTAYMELRSLTSVDAAVYYCARDHRYN EGVSFDYWGQGTTLTVSSGGGGSGGGGSGGGGSGGGGSNIVLTQSPASLAVS LGQRATISCRASESVDGFGNSFMNWYQQKPGQSPKLLIYLASNLESGVPARFS GSGSRTDFTLTIDPVEADDAATYYCQQNNEDPYTFGGGTKLEIKR (SEQ ID NO: 51).
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 51.
  • the polypeptide comprises a sequence that is at least 90% identical to a sequence of SEQ ID NO: 51.
  • the polypeptide comprises a sequence that is at least 95% identical to a sequence of SEQ ID NO: 51.
  • the polypeptide comprises a sequence that is at least 99% identical to a sequence of SEQ ID NO: 51.
  • the polypeptide comprises a sequence as set forth in SEQ ID NO: 51.
  • the polypeptide as set forth in SEQ ID NO: 51 is an antibody, or an antigen binding fragment thereof.
  • the antibody is an anti-CD8 antibody.
  • the anti-CD8 antibody binds to non- human primate CD8.
  • the anti-CD8 antibody binds to human CD8.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 50 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3) as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 50 and comprises a stalk portion (S1) comprising a flexible polypeptide further comprising a polypeptide comprising a transmembrane domain as provided for herein.
  • the flexible polypeptide further comprising a polypeptide comprising a transmembrane domain is represented by the -124- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT formula L3-X1, wherein L3 is a flexible polypeptide as provided for herein and X1 is a polypeptide comprising a transmembrane domain as provided for herein.
  • X1 may comprise a polypeptide having the formula of ECD-TM-ICD, wherein ECD is an extracellular domain, or fragment thereof as provided for herein, or is absent; TM is a transmembrane domain as provided for herein; and ICD is an intracellular domain as provided for herein or is absent.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 50 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 50 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 50 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 50 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 50 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 50 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 50 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, -125- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 50 and comprising a stalk portion (S1) comprising a flexible polypeptide (L3- X1) comprising an ECD, a TM, and an ICD, is anchored to the surface of a viral particle, such as those provided for herein .
  • the identities of L3, ECD, TM, and ICD are as provided for herein.
  • thepolypeptide bind to an immune cell, such as those provided herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 51 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3) as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 51 and comprises a stalk portion (S1) comprising a flexible polypeptide further comprising a polypeptide comprising a transmembrane domain as provided for herein.
  • the flexible polypeptide further comprising a polypeptide comprising a transmembrane domain is represented by the formula L3-X1, wherein L3 is a flexible polypeptide as provided for herein and X1 is a polypeptide comprising a transmembrane domain as provided for herein.
  • X1 may comprise a polypeptide having the formula of ECD-TM-ICD, wherein ECD is an extracellular domain, or fragment thereof as provided for herein, or is absent; TM is a transmembrane domain as provided for herein; and ICD is an intracellular domain as provided for herein or is absent.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 51 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 51 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 51 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD.
  • the -126- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 51 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 51 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 51 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 51 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of SEQ ID NO: 51 and comprising a stalk portion (S1) comprising a flexible polypeptide (L3- X1) comprising an ECD, a TM, and an ICD, is anchored to the surface of a viral particle, such as those provided for herein .
  • the identities of L3, ECD, TM, and ICD are as provided for herein.
  • thepolypeptide bind to an immune cell, such as those provided herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 50 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3) as provided for herein. In some embodiments, the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 50 and comprises a stalk portion (S1) comprising a flexible polypeptide further comprising a polypeptide comprising a transmembrane domain as provided for herein.
  • the flexible polypeptide further comprising a polypeptide comprising a transmembrane domain is represented by the formula L3-X1, wherein L3 is a flexible polypeptide as provided for herein and X1 is a polypeptide comprising a transmembrane domain as provided for herein.
  • X1 may comprise a -127- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT polypeptide having the formula of ECD-TM-ICD, wherein ECD is an extracellular domain, or fragment thereof as provided for herein, or is absent; TM is a transmembrane domain as provided for herein; and ICD is an intracellular domain as provided for herein or is absent.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 50 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 50 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 50 and comprises a stalk portion (S 1 ) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 50 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 50 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 50 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 50 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprising a sequence having a sequence as set forth in SEQ ID NO: 50 and comprising a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a TM, and an ICD is anchored to the surface of a viral particle, such as those provided for herein .
  • the identities of L3, ECD, TM, and ICD are as provided for herein.
  • the polypeptide bind to an immune cell, such as those provided herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 51 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3) as provided for herein.
  • the polypeptide comprises a sequence -128- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT having a sequence as set forth in SEQ ID NO: 51 and comprises a stalk portion (S1) comprising a flexible polypeptide further comprising a polypeptide comprising a transmembrane domain as provided for herein.
  • the flexible polypeptide further comprising a polypeptide comprising a transmembrane domain is represented by the formula L3-X1, wherein L3 is a flexible polypeptide as provided for herein and X1 is a polypeptide comprising a transmembrane domain as provided for herein.
  • X1 may comprise a polypeptide having the formula of ECD-TM-ICD, wherein ECD is an extracellular domain, or fragment thereof as provided for herein, or is absent; TM is a transmembrane domain as provided for herein; and ICD is an intracellular domain as provided for herein, or is absent.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 51 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 51 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 51 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 51 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 51 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 51 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprises a sequence having a sequence as set forth in SEQ ID NO: 51 and comprises a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising a CD8 and/or CD28 ECD, a CD8 and/or CD28 TM, and an ICD, wherein the ICD comprises an Env incorporation motif as provided for herein.
  • the polypeptide comprising a sequence having a sequence as set forth in SEQ ID NO: 51 and comprising a stalk portion (S1) comprising a flexible polypeptide (L3-X1) comprising an ECD, a TM, and an ICD, is anchored to the surface of a -129- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT viral particle, such as those provided for herein .
  • the identities of L3, ECD, TM, and ICD are as provided for herein.
  • the polypeptide bind to an immune cell, such as those provided herein.
  • the viral particle comprising a heterologous viral glycoprotein and a targeting moiety further comprises a nucleic acid molecule encoding for a heterologous molecule of interest or “cargo.”
  • the heterologous viral glycoprotein is as provided for herein.
  • the targeting moiety is as provided for herein.
  • heterologous molecule of interest is meant to refer to any product that may be encoded by a nucleic acid molecule.
  • “cargo” or “heterologous molecule of interest” may refer to an siRNA, an shRNA, a peptide, a polypeptide, a protein, a viral payload, a viral genome, or a combination thereof.
  • the heterologous molecule of interest is an siRNA, an shRNA, a non-coding RNA (e.g. a guide RNA for a CRISPR system), a peptide, a polypeptide, a protein, a viral payload, a viral genome, a chimeric antigen receptor (“CAR”), or a combination thereof.
  • the polypeptide is a CAR.
  • a “chimeric antigen receptor” or “CAR” as used herein refers to an antigen-binding domain that is fused, directly, or indirectly (e.g. via a hinge or transmembrane domain to an intracellular signaling domain capable of activating or stimulating an immune cell.
  • the CAR's extracellular binding domain is composed of a single chain variable fragment (scFv) derived from fusing the variable heavy and light regions of a murine or humanized monoclonal antibody.
  • scFvs may be used that are derived from Fab's (instead of from an antibody, e.g., obtained from Fab libraries).
  • this scFv is fused to a transmembrane domain and then to an intracellular signaling domain.
  • the antigen binding domain can be any molecule that can bind to the target on the cell.
  • the antigen binding domain of a CAR can be an antibody, a scFv antibody, an antigen binding domain, an ankyrin repeat (e.g.
  • a VHH domain antibody includes those that solely provide CD3 ⁇ signals upon antigen binding.
  • the CAR includes those that provide both -130- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT costimulation (e.g. CD28 or CD137) and activation (CD3 ⁇ ). In some embodiments, the CARs include those that provide multiple costimulation (e.g. CD28 and CD137) and activation (CD3 ⁇ ). In various embodiments, the CAR is selected to have high affinity or avidity for the antigen. In some embodiments, the antigen-binding domain binds to CD19. In some embodiments, the antigen-binding domain comprises a CD19 antibody, or fragment thereof.
  • antibody fragments are as provided for herein, such as but not limited to a scFv antibody, an antigen binding domain, an ankyrin repeat (e.g. DARPIN), a VHH domain antibody, a nanobody, single domain antibody, a FN3 domain, or any combination thereof.
  • the antigen-binding domain of the CAR comprises an antibody, or antigen binding fragment thereof, wherein the antibody or antigen binding fragment comprises a peptide selected from the following table, which illustrates the CDRs based on Chothia numbering.
  • the antigen-binding domain of the CAR comprises a heavy or light chain CDR as provided in the tables above. In some embodiments, the antigen- binding domain of the CAR comprises a heavy or light chain CDR as provided in the tables above and binds to non-human primate CD19. In some embodiments, the antigen-binding domain of the CAR comprises a heavy or light chain CDR as provided in the tables above and binds to human CD19. In some embodiments, a polypeptide, the antigen-binding domain of the CAR comprises a light chain CDR having a sequence selected from SEQ ID NO: 111-113.
  • the antigen-binding domain of the CAR comprises a light chain CDR having a sequence of SEQ ID NO: 111. In some embodiments, the antigen-binding domain of the CAR comprises a light chain CDR having a sequence of SEQ ID NO: 112. In some embodiments, the antigen-binding domain of the CAR comprises a light chain CDR having a sequence of SEQ ID NO: 113. In some embodiments, the antigen-binding domain of the CAR comprises a heavy chain CDR having a sequence selected from SEQ ID NO: 108-110. In some embodiments, the antigen-binding domain of the CAR comprises a heavy chain CDR having a sequence of SEQ ID NO: 108.
  • the antigen-binding domain of the CAR comprises a heavy chain CDR having a sequence of SEQ ID NO: 109.
  • -131- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT the antigen-binding domain of the CAR comprises a heavy chain CDR having a sequence of SEQ ID NO: 110.
  • the CDRs referenced in the embodiments throughout the present specification can be interchanged with the CDRs that are characterized by different formats, such as Kabat and IMGT.
  • the antigen-binding domain of the CAR comprises a light chain variable region having a LCDR1, a LCDR2, and a LCDR3, wherein the LCDR1 has a sequence of SEQ ID NO: 111, the LCDR2 has a sequence of SEQ ID NO: 112, and the LCDR3 has a sequence of SEQ ID NO: 113.
  • the antigen-binding domain of the CAR comprises a heavy chain variable region having a HCDR1, a HCDR2, and a HCDR3, wherein the HCDR1 has a sequence of SEQ ID NO: 108, the HCDR2 has a sequence of SEQ ID NO: 109, and the HCDR3 has a sequence of SEQ ID NO: 110.
  • the antigen-binding domain of the CAR comprises: (i) a light chain having any one of the foregoing recited combinations of LCDR1, LCDR2, and LCDR3 sequences; and (ii) a heavy chain having any one of the foregoing recited combinations of HCDR1, HCDR2, and HCDR3 sequences.
  • the different CDR motifs can be combined in any combination including those not depicted in the table above. For example, the following embodiments are provided as non- limiting examples of such combinations.
  • the antigen-binding domain of the CAR comprises: (i) a light chain variable region comprising light chain CDRl, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 111; the light chain CDR2 has the amino acid sequence of SEQ ID NO: 112; and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 113; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 108; the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 109; and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 110; or variants of any of the foregoing.
  • the equivalent CDR sequences can be used from the IMGT and Kabat designations.
  • the light chain variable region CDR1 is replaced with any of the other light chain CDR1 sequences.
  • the light chain variable region CDR2 is replaced with any of the other light chain CDR2 sequences.
  • -132- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT the light chain variable region CDR3 is replaced with any of the other light chain CDR3 sequences.
  • the heavy chain variable region CDR1 is replaced with any of the other heavy chain CDR1 sequences.
  • the heavy chain variable region CDR2 is replaced with any of the other heavy chain CDR2 sequences.
  • the heavy chain variable region CDR3 is replaced with any of the other heavy chain CDR3 sequences.
  • the antigen-binding domain of the CAR comprises a VH domain, a VL domain, or a VH and a VL domain.
  • the VH domain comprises an amino acid sequence having at least 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 89, or any value or range in-between.
  • the VH domain comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 89. In some embodiments, the VH domain comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 89. In some embodiments, the VH domain comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 89.
  • the VH domain comprises an amino acid sequence having at least 99% identity to SEQ ID NO: 89. In some embodiments, the VH domain comprises an amino acid sequence having the sequence of SEQ ID NO: 89. In some embodiments, the VL domain comprises an amino acid sequence having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 90, or any value or range in-between.
  • the VL domain comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 90. In some embodiments, the VL domain comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 90. In some embodiments, the VL domain comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 90. In some embodiments, the VL domain comprises an amino acid sequence having at least 99% identity to SEQ ID NO: 90.
  • the VL domain comprises an amino acid sequence having the sequence of SEQ ID NO: 90. -133- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT
  • the antigen-binding domain of the CAR comprises a VH domain and a VL domain.
  • the VH and VL domain are not linked by a linker peptide.
  • the VH and VL domain are linked by a linker peptide, such as those as provided for herein, including but not limited to: (GGGGS)n (SEQ ID NO: 55), wherein each n is independently 1-5.
  • n is 1.
  • n is 2.
  • n is 3.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 89, and comprises a V L having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 90.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 89, and comprises a VL having at least 90% identity to SEQ ID NO: 90.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 89, and comprises a VL having at least 95% identity to SEQ ID NO: 90.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 89, and comprises a VL having at least 98% identity to SEQ ID NO: 90.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 89, and comprises a VL having at least 99% identity to SEQ ID NO: 90.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 89, and comprises a VL having the sequence of SEQ ID NO: 90.
  • the antigen- binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 90% identity to SEQ ID NO: 89, and comprises a VL having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 90.
  • the antigen-binding domain of the CAR -134- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT comprising a VH domain and a VL domain comprises a VH domain having at least 95% identity to SEQ ID NO: 89, and comprises a VL having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 90.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 98% identity to SEQ ID NO: 89, and comprises a VL having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 90.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 99% identity to SEQ ID NO: 89, and comprises a VL having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 90.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having an amino acid sequence of SEQ ID NO: 89, and comprises a VL having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 90.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 90% identity to SEQ ID NO: 89, and comprises a VL having at least 90% identity to SEQ ID NO: 90.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 95% identity to SEQ ID NO: 89, and comprises a VL having at least 90% identity to SEQ ID NO: 90. In some embodiments, the antigen- binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 90% identity to SEQ ID NO: 89, and comprises a VL having at least 95% identity to SEQ ID NO: 90.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 95% identity to SEQ ID NO: 89, and comprises a VL having at least 95% identity to SEQ ID NO: 90. In some embodiments, the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 98% identity to SEQ ID NO: 89, and comprises a VL having at least 98% identity to SEQ ID NO: 90.
  • the antigen- binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 99% identity to SEQ ID NO: 89, and comprises a VL having at least 99% identity to SEQ ID NO: 90.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having an amino acid sequence of SEQ ID NO: 89, and comprises a VL having an amino acid sequence of SEQ ID NO: 90.
  • the antigen-binding domain of the CAR comprises a formula of VH-Z-VL, wherein VH is a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 89, Z is a linker comprising the amino acid sequence GGGGSGGGGSGGGGS (SEQ ID NO: 91), and VL is a light chain variable region comprising the amino acid sequence of SEQ ID NO: 90.
  • the antigen-binding domain of the CAR comprising a formula of VH-Z-VL has an amino acid sequence as set forth below: EVQLVQSGAEVKKPGESLKISCKGSGYSFSSSWIGWVRQMPGKGLEWMGIIY PDDSDTRYSPSFQGQVTISADKSIRTAYLQWSSLKASDTAMYYCARHVTMIW GVIIDFWGQGTLVTVSSGGGGSGGGGSGGGGSAIQLTQSPSSLSASVGDRVT ITCRASQGISSALAWYQQKPGKAPKLLIYDASSLESGVPSRFSGSGSGTDFT LTISSLQPEDFATYYCQQFNSYPYTFGQGTKLEIK (SEQ ID NO: 92)
  • the antigen-binding domain of the CAR comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 9
  • the antigen-binding domain of the CAR comprises an amino acid sequence having at least 90% identity to a sequence of SEQ ID NO: 92. In some embodiments, the antigen-binding domain of the CAR comprises an amino acid sequence having at least 95% identity to a sequence of SEQ ID NO: 92. In some embodiments, the antigen-binding domain of the CAR comprises an amino acid sequence having at least 98% identity to a sequence of SEQ ID NO: 92. In some embodiments, the antigen-binding domain of the CAR comprises an amino acid sequence having at least 99% identity to a sequence of SEQ ID NO: 92. In some embodiments, the antigen-binding domain of the CAR comprises the amino acid sequence of SEQ ID NO: 92.
  • the antigen-binding domain of the CAR comprises a formula of VL-Z-VH, wherein VL is a light chain variable region comprising the amino acid sequence of SEQ ID NO: 90, Z is a linker comprising the amino acid sequence GGGGSGGGGSGGGGS (SEQ ID NO: 91), and VH is a light chain variable region comprising the amino acid sequence of SEQ ID NO: 89.
  • the antigen-binding domain of the CAR comprising a formula of VL-Z-VH has an amino acid sequence as set forth below: AIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQQKPGKAPKLLIYDAS SLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNSYPYTFGQGTKL EIKGGGGSGGGGSGGGGSEVQLVQSGAEVKKPGESLKISCKGSGYSFSSSWI GWVRQMPGKGLEWMGIIYPDDSDTRYSPSFQGQVTISADKSIRTAYLQWSSL KASDTAMYYCARHVTMIWGVIIDFWGQGTLVTVSS (SEQ ID NO: 93) -136- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT
  • the antigen-binding domain of the CAR comprises an amino acid sequence having at least 70%, 75%, 80%, 85%,
  • the antigen-binding domain of the CAR comprises an amino acid sequence having at least 90% identity to a sequence of SEQ ID NO: 93. In some embodiments, the antigen-binding domain of the CAR comprises an amino acid sequence having at least 95% identity to a sequence of SEQ ID NO: 93. In some embodiments, the antigen-binding domain of the CAR comprises an amino acid sequence having at least 98% identity to a sequence of SEQ ID NO: 93. In some embodiments, the antigen-binding domain of the CAR comprises an amino acid sequence having at least 99% identity to a sequence of SEQ ID NO: 93. In some embodiments, the antigen-binding domain of the CAR comprises the amino acid sequence of SEQ ID NO: 93.
  • the antigen-binding domain of the CAR comprises an antibody, or antigen binding fragment thereof, wherein the antibody or antigen binding fragment comprises a peptide selected from the following table, which illustrates the CDRs based on Chothia numbering. Chothia CDRs Ab ID No HCDR1 HCDR2 HCDR3 LCDR1 LCDR2 LCDR3
  • the antigen-binding domain of the CAR comprises a heavy or light chain CDR as provided in the tables above.
  • the antigen- binding domain of the CAR comprises a heavy or light chain CDR as provided in the tables above and binds to non-human primate CD19.
  • the antigen-binding domain of the CAR comprises a heavy or light chain CDR as provided in the tables above and binds to human CD19.
  • a polypeptide the antigen-binding domain of the CAR comprises a light chain CDR having a sequence selected from SEQ ID NO: 117-119.
  • the antigen-binding domain of the CAR comprises a light chain CDR having a sequence of SEQ ID NO: 117.
  • the antigen-binding domain of the CAR comprises a light chain CDR having a sequence of SEQ ID NO: 118.
  • the antigen-binding domain of the CAR comprises a light chain CDR having a sequence of SEQ ID NO: 119. In some embodiments, the antigen-binding domain of the CAR comprises a heavy chain CDR having a sequence selected from SEQ ID NO: 114-116. In some -137- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT embodiments, the antigen-binding domain of the CAR comprises a heavy chain CDR having a sequence of SEQ ID NO: 114. In some embodiments, the antigen-binding domain of the CAR comprises a heavy chain CDR having a sequence of SEQ ID NO: 115.
  • the antigen-binding domain of the CAR comprises a heavy chain CDR having a sequence of SEQ ID NO: 116.
  • the CDRs referenced in the embodiments throughout the present specification can be interchanged with the CDRs that are characterized by different formats, such as Kabat and IMGT.
  • the antigen-binding domain of the CAR comprises a light chain variable region having a LCDR1, a LCDR2, and a LCDR3, wherein the LCDR1 has a sequence of SEQ ID NO: 117, the LCDR2 has a sequence of SEQ ID NO: 118, and the LCDR3 has a sequence of SEQ ID NO: 119.
  • the antigen-binding domain of the CAR comprises a heavy chain variable region having a HCDR1, a HCDR2, and a HCDR3, wherein the HCDR1 has a sequence of SEQ ID NO: 114, the HCDR2 has a sequence of SEQ ID NO: 115, and the HCDR3 has a sequence of SEQ ID NO: 116.
  • the antigen-binding domain of the CAR comprises: (i) a light chain having any one of the foregoing recited combinations of LCDR1, LCDR2, and LCDR3 sequences; and (ii) a heavy chain having any one of the foregoing recited combinations of HCDR1, HCDR2, and HCDR3 sequences.
  • the antigen-binding domain of the CAR comprises: (i) a light chain variable region comprising light chain CDRl, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 117; the light chain CDR2 has the amino acid sequence of SEQ ID NO: 118; and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 119; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 114; the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 115; and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 116; or variants of any of the fore
  • the equivalent CDR sequences can be used from the IMGT and Kabat designations. -138- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT
  • the light chain variable region CDR1 is replaced with any of the other light chain CDR1 sequences.
  • the light chain variable region CDR2 is replaced with any of the other light chain CDR2 sequences.
  • the light chain variable region CDR3 is replaced with any of the other light chain CDR3 sequences.
  • the heavy chain variable region CDR1 is replaced with any of the other heavy chain CDR1 sequences.
  • the heavy chain variable region CDR2 is replaced with any of the other heavy chain CDR2 sequences.
  • the heavy chain variable region CDR3 is replaced with any of the other heavy chain CDR3 sequences.
  • the antigen-binding domain of the CAR comprises a V H domain, a VL domain, or a VH and a VL domain.
  • the VH domain comprises an amino acid sequence having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 94, or any value or range in-between.
  • the VH domain comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 94. In some embodiments, the VH domain comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 94. In some embodiments, the VH domain comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 94.
  • the VH domain comprises an amino acid sequence having at least 99% identity to SEQ ID NO: 94. In some embodiments, the VH domain comprises an amino acid sequence having the sequence of SEQ ID NO: 94. In some embodiments, the VL domain comprises an amino acid sequence having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 95, or any value or range in-between.
  • the VL domain comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 95. In some embodiments, the VL domain comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 95. In some embodiments, the VL domain comprises an amino acid sequence having at least 98% identity to SEQ ID NO: -139- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT 95.
  • the VL domain comprises an amino acid sequence having at least 99% identity to SEQ ID NO: 95. In some embodiments, the VL domain comprises an amino acid sequence having the sequence of SEQ ID NO: 95. In some embodiments, the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 94, and comprises a VL having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 95.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a V H domain having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 94, and comprises a VL having at least 90% identity to SEQ ID NO: 95.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 94, and comprises a VL having at least 95% identity to SEQ ID NO: 95.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 94, and comprises a VL having at least 98% identity to SEQ ID NO: 95.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 94, and comprises a VL having at least 99% identity to SEQ ID NO: 95.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 94, and comprises a VL having the sequence of SEQ ID NO: 95.
  • the antigen- binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 90% identity to SEQ ID NO: 94, and comprises a VL having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 95.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 95% identity to SEQ ID NO: 94, and comprises a VL having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 95.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 98% identity to SEQ ID NO: 94, and comprises a VL having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 95.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 99% identity to SEQ ID NO: 94, and comprises a VL having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 95.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having an amino acid sequence of SEQ ID NO: 94, and comprises a V L having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 95.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 90% identity to SEQ ID NO: 94, and comprises a VL having at least 90% identity to SEQ ID NO: 95.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 95% identity to SEQ ID NO: 94, and comprises a VL having at least 90% identity to SEQ ID NO: 95. In some embodiments, the antigen- binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 90% identity to SEQ ID NO: 94, and comprises a VL having at least 95% identity to SEQ ID NO: 95.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 95% identity to SEQ ID NO: 94, and comprises a VL having at least 95% identity to SEQ ID NO: 95. In some embodiments, the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 98% identity to SEQ ID NO: 94, and comprises a VL having at least 98% identity to SEQ ID NO: 95.
  • the antigen- binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having at least 99% identity to SEQ ID NO: 94, and comprises a VL having at least 99% identity to SEQ ID NO: 95.
  • the antigen-binding domain of the CAR comprising a VH domain and a VL domain comprises a VH domain having an amino acid sequence of SEQ ID NO: 94, and comprises a VL having an amino acid sequence of SEQ ID NO: 95.
  • the antigen-binding domain of the CAR comprises a formula of VH-Z-VL, wherein VH is a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 94, Z is a linker comprising the amino acid sequence GGGGSGGGGSGGGGS (SEQ ID NO: 91), and VL is a light chain variable region comprising the amino acid sequence -141- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT of SEQ ID NO: 95.
  • the antigen-binding domain of the CAR comprising a formula of VH-Z-VL has an amino acid sequence as set forth below: QVQLVQSGAEVKKPGSSVKVSCKDSGGTFSSYAISWVRQAPGQGLEWMGGII PIFGTTNYAQQFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREAVAAD WLDPWGQGTLVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLS CRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTL TISRLEPEDFAVYYCQQYGSSRFTFGPGTKVDIK (SEQ ID NO: 96)
  • the antigen-binding domain of the CAR comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%
  • the antigen-binding domain of the CAR comprises an amino acid sequence having at least 90% identity to a sequence of SEQ ID NO: 96. In some embodiments, the antigen-binding domain of the CAR comprises an amino acid sequence having at least 95% identity to a sequence of SEQ ID NO: 96. In some embodiments, the antigen-binding domain of the CAR comprises an amino acid sequence having at least 98% identity to a sequence of SEQ ID NO: 96. In some embodiments, the antigen-binding domain of the CAR comprises an amino acid sequence having at least 99% identity to a sequence of SEQ ID NO: 96. In some embodiments, the antigen-binding domain of the CAR comprises the amino acid sequence of SEQ ID NO: 96.
  • the antigen-binding domain of the CAR comprises a formula of VL-Z-VH, wherein VL is a light chain variable region comprising the amino acid sequence of SEQ ID NO: 95, Z is a linker comprising the amino acid sequence GGGGSGGGGSGGGGS (SEQ ID NO: 91), and VH is a light chain variable region comprising the amino acid sequence of SEQ ID NO: 94.
  • the antigen-binding domain of the CAR comprising a formula of VL-Z-VH has an amino acid sequence as set forth below: EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGA SSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSRFTFGPGTK VDIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGSSVKVSCKDSGGTFSSYA ISWVRQAPGQGLEWMGGIIPIFGTTNYAQQFQGRVTITADESTSTAYMELSS LRSEDTAVYYCAREAVAADWLDPWGQGTLVTVSS (SEQ ID NO: 97)
  • the antigen-binding domain of the CAR comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 9
  • the antigen-binding domain of the CAR comprises an amino acid sequence having at least 90% identity to a sequence of SEQ ID NO: 97. In some embodiments, the antigen-binding domain of the CAR comprises an amino acid sequence having at least 95% -142- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT identity to a sequence of SEQ ID NO: 97. In some embodiments, the antigen-binding domain of the CAR comprises an amino acid sequence having at least 98% identity to a sequence of SEQ ID NO: 97. In some embodiments, the antigen-binding domain of the CAR comprises an amino acid sequence having at least 99% identity to a sequence of SEQ ID NO: 97.
  • the antigen-binding domain of the CAR comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the antigen-binding domain of the CAR comprises any anti- CD19 antibody, or an scFv thereof, or an active fragment thereof.
  • the antigen-binding domain of the CAR comprises axicabtagene ciloleucel (KTEX19, Yescarta), brexucabtagene autoleucel (Tecartus), lisocabtagene maraleucel (JCAR017, Breyanzi), tisagenlecleucel (CTL019, Kymriah), tafasitamab (MOR208, XmAb5574, Monjuvi), loncastuximab tesirine (ADCT-402), anti-CD19 antibody clone 21D4, 21D4a, 47G4, FMC63, SJ25C1, inebilizumab, blinatumomab (MT103, AMG103, Blincyto), coltuximab ravtansine (SAR3419), MEDI-551, Denintuzumab mafodotin (SGN-CD19A), taplitumomabpapto
  • the antigen binding domain of the CAR is an antibody, or an scFv thereof, or an active fragment thereof, as provided in U.S. Patent Serial No. 8,097,703B2, U.S. Patent Serial No. 10,287,350B2, U.S. Patent Serial No.11,236,161B2, U.S. Patent Publication No.2022/0153838A1, and U.S. Patent Publication No.2022/0204619A1; each of which are hereby incorporated by reference in their entirety.
  • the CAR comprises the 4-1BB domain as well.
  • the antigen binding domain of the CAR comprises a VH and a VL as provided for herein.
  • the antigen binding domain of the CAR comprises a VH and/or a VL as provided in the table below.
  • the CAR comprises
  • the CAR comprises a VL selected from SEQ ID NO: 90, SEQ ID NO: 95, SEQ ID NO: 134, SEQ ID NO: 136, SEQ ID NO: 138, SEQ ID NO: 140, SEQ ID NO: 142, SEQ ID NO: 144, SEQ ID NO: 146, SEQ ID NO: 148, SEQ ID NO: 150, SEQ ID NO: 152, SEQ ID NO: 154, SEQ ID NO: 156, or SEQ ID NO: 158.
  • the CAR comprises a VH selected from SEQ ID NO: 89, SEQ ID NO: 94, SEQ ID NO: 133, SEQ ID NO: 135, SEQ ID NO: 137, SEQ ID NO: 139, SEQ ID NO: 141, SEQ ID NO: 143, SEQ ID NO: 145, SEQ ID NO: 147, SEQ ID NO: 149, SEQ ID NO: 151, SEQ ID NO: 153, SEQ ID NO: 155, or SEQ ID NO: 157 and a VL selected from SEQ ID NO: 90, SEQ ID NO: 95, SEQ ID NO: 134, SEQ ID NO: 136, SEQ ID NO: 138, SEQ ID NO: 140, SEQ ID NO: 142, SEQ ID NO: 144, SEQ ID NO: 146, SEQ ID NO: 148, SEQ ID NO: 150, SEQ ID NO: 152, SEQ ID NO: 154, SEQ ID NO: 156, or SEQ ID NO:
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence as provided in the following table: CAR ID No. SEQ ID Sequence NO.
  • the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 99. In some embodiments, the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 99. In some embodiments, the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ -149- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT ID NO: 99. In some embodiments, the CAR comprises an amino acid sequence of SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 99, wherein the antigen binding domain of the CAR corresponds to amino acids 24-266 of SEQ ID NO: 99. In some embodiments, the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 99, wherein the antigen binding domain of the CAR corresponds to amino acids 24-266 of SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 99, wherein the antigen binding domain of the CAR corresponds to amino acids 24-266 of SEQ ID NO: 99. In some embodiments, the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 99, wherein the antigen binding domain of the CAR corresponds to amino acids 24-266 of SEQ ID NO: 99. In some embodiments, the CAR comprises an amino acid sequence of SEQ ID NO: 99, wherein the antigen binding domain of the CAR corresponds to amino acids 24-266 of SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 99, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VH corresponds to amino acids 24-144 of SEQ ID NO: 99 and the VL corresponds to amino acids 160-266 of SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 99, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VH corresponds to amino acids 24-144 of SEQ ID NO: 99 and the VL corresponds to amino acids 160-266 of SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 99, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VH corresponds to amino acids 24-144 of SEQ ID NO: 99 and the VL corresponds to amino acids 160-266 of SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 99, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VH corresponds to amino acids 24-144 of SEQ ID NO: 99 and the VL corresponds to amino acids 160-266 of SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence of SEQ ID NO: 99, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VH corresponds to -150- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT amino acids 24-144 of SEQ ID NO: 99 and the VL corresponds to amino acids 160-266 of SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 99, wherein the antigen binding domain of the CAR corresponds to amino acids 24-266 of SEQ ID NO: 99, a hinge domain of the CAR corresponds to amino acids 271-325 of SEQ ID NO: 99, a transmembrane domain of the CAR corresponds to amino acids 326-353 of SEQ ID NO: 99, a costimulatory domain of the CAR corresponds to amino acids 354-395 of SEQ ID NO: 99, and a signaling domain of the CAR corresponds to amino acids 396-507 of SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 99, wherein the antigen binding domain of the CAR corresponds to amino acids 24-266 of SEQ ID NO: 99, a hinge domain of the CAR corresponds to amino acids 271-325 of SEQ ID NO: 99, a transmembrane domain of the CAR corresponds to amino acids 326-353 of SEQ ID NO: 99, a costimulatory domain of the CAR corresponds to amino acids 354-395 of SEQ ID NO: 99, and a signaling domain of the CAR corresponds to amino acids 396-507 of SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 99, wherein the antigen binding domain of the CAR corresponds to amino acids 24-266 of SEQ ID NO: 99, a hinge domain of the CAR corresponds to amino acids 271-325 of SEQ ID NO: 99, a transmembrane domain of the CAR corresponds to amino acids 326-353 of SEQ ID NO: 99, a costimulatory domain of the CAR corresponds to amino acids 354-395 of SEQ ID NO: 99, and a signaling domain of the CAR corresponds to amino acids 396-507 of SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 99, wherein the antigen binding domain of the CAR corresponds to amino acids 24-266 of SEQ ID NO: 99, a hinge domain of the CAR corresponds to amino acids 271-325 of SEQ ID NO: 99, a transmembrane domain of the CAR corresponds to amino acids 326-353 of SEQ ID NO: 99, a costimulatory domain of the CAR corresponds to amino acids 354-395 of SEQ ID NO: 99, and a signaling domain of the CAR corresponds to amino acids 396-507 of SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence of SEQ ID NO: 99, wherein the antigen binding domain of the CAR corresponds to amino acids 24-266 of SEQ ID NO: 99, the hinge domain of the CAR corresponds to amino acids 271-325 of SEQ ID NO: 99, the transmembrane domain of the CAR corresponds to amino acids 326-353 of SEQ ID NO: 99, -151- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT the costimulatory domain of the CAR corresponds to amino acids 354-395 of SEQ ID NO: 99, and the signaling domain of the CAR corresponds to amino acids 396-507 of SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 99, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VH corresponds to amino acids 24-144 of SEQ ID NO: 99 and the VL corresponds to amino acids 160-266 of SEQ ID NO: 99, a hinge domain of the CAR corresponds to amino acids 271-325 of SEQ ID NO: 99, a transmembrane domain of the CAR corresponds to amino acids 326-353 of SEQ ID NO: 99, a costimulatory domain of the CAR corresponds to amino acids 354-395 of SEQ ID NO: 99, and a signaling domain of the CAR corresponds to amino acids 396-507 of SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 99, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VH corresponds to amino acids 24-144 of SEQ ID NO: 99 and the VL corresponds to amino acids 160-266 of SEQ ID NO: 99, a hinge domain of the CAR corresponds to amino acids 271-325 of SEQ ID NO: 99, a transmembrane domain of the CAR corresponds to amino acids 326-353 of SEQ ID NO: 99, a costimulatory domain of the CAR corresponds to amino acids 354-395 of SEQ ID NO: 99, and a signaling domain of the CAR corresponds to amino acids 396-507 of SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 99, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VH corresponds to amino acids 24-144 of SEQ ID NO: 99 and the VL corresponds to amino acids 160-266 of SEQ ID NO: 99, a hinge domain of the CAR corresponds to amino acids 271-325 of SEQ ID NO: 99, a transmembrane domain of the CAR corresponds to amino acids 326-353 of SEQ ID NO: 99, a costimulatory domain of the CAR corresponds to amino acids 354-395 of SEQ ID NO: 99, and a signaling domain of the CAR corresponds to amino acids 396-507 of SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 99, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VH corresponds to amino acids 24-144 of SEQ ID NO: 99 and the VL corresponds to amino acids 160-266 of SEQ ID NO: 99, a hinge domain of the CAR corresponds to amino acids 271-325 of SEQ ID NO: 99, a transmembrane domain of the CAR corresponds to amino acids 326-353 of SEQ ID NO: 99, a costimulatory domain of the CAR corresponds to amino acids 354-395 of SEQ ID NO: 99, and a signaling domain of the CAR corresponds to amino acids 396-507 of SEQ ID NO: 99.
  • the CAR -152- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT comprises an amino acid sequence of SEQ ID NO: 99, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VH corresponds to amino acids 24-144 of SEQ ID NO: 99 and the VL corresponds to amino acids 160-266 of SEQ ID NO: 99, the hinge domain of the CAR corresponds to amino acids 271-325 of SEQ ID NO: 99, the transmembrane domain of the CAR corresponds to amino acids 326-353 of SEQ ID NO: 99, the costimulatory domain of the CAR corresponds to amino acids 354-395 of SEQ ID NO: 99, and the signaling domain of the CAR corresponds to amino acids 396-507 of SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 99
  • the antigen binding domain of the CAR comprises an amino acid sequence of SEQ ID NO: 92 and corresponds to amino acids 24-266 of SEQ ID NO: 99
  • a hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 271-325 of SEQ ID NO: 99
  • a transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 326-353 of SEQ ID NO: 99
  • a costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 354-395 of SEQ ID NO: 99
  • a signaling domain of the CAR comprises an amino acid sequence of SEQ ID
  • the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 99, wherein the antigen binding domain of the CAR comprises an amino acid sequence of SEQ ID NO: 92 and corresponds to amino acids 24-266 of SEQ ID NO: 99, a hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 271-325 of SEQ ID NO: 99, a transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 32
  • the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 99, wherein -153- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT
  • the antigen binding domain of the CAR comprises an amino acid sequence of SEQ ID NO: 92 and corresponds to amino acids 24-266 of SEQ ID NO: 99
  • the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 271-325 of SEQ ID NO: 99
  • the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 326-353 of SEQ ID NO: 99
  • the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 354-395 of SEQ ID NO: 99
  • the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 396- 507 of SEQ ID NO
  • the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 99, wherein the antigen binding domain of the CAR comprises an amino acid sequence of SEQ ID NO: 92 and corresponds to amino acids 24-266 of SEQ ID NO: 99, the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 271-325 of SEQ ID NO: 99, the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 326-353 of SEQ ID NO: 99, the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 354- 395 of SEQ ID NO: 99, and the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 396-507 of SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence of SEQ ID NO: 99
  • the antigen binding domain of the CAR comprises an amino acid sequence of SEQ ID NO: 92 and corresponds to amino acids 24-266 of SEQ ID NO: 99
  • the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 271-325 of SEQ ID NO: 99
  • the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 326-353 of SEQ ID NO: 99
  • the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 354-395 of SEQ ID NO: 99
  • the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 396- 507 of SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 99, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VH comprises an amino acid sequence of SEQ ID NO: 89 and corresponds to amino acids 24-144 of SEQ ID NO: 99 and the VL comprises an amino acid sequence of SEQ ID NO: 90 and corresponds to amino acids 160-266 of SEQ ID NO: 99, -154- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT a hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 271-325 of SEQ ID NO: 99, a transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds
  • the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 99
  • the VH comprises an amino acid sequence of SEQ ID NO: 89 and corresponds to amino acids 24-144 of SEQ ID NO: 99 and the VL comprises an amino acid sequence of SEQ ID NO: 90 and corresponds to amino acids 160-266 of SEQ ID NO: 99
  • the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 271-325 of SEQ ID NO: 99
  • the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 326-353 of SEQ ID NO: 99
  • the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 354-395 of SEQ ID NO: 99
  • the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 396- 507 of SEQ ID NO: 99
  • the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 99
  • the VH comprises an amino acid sequence of SEQ ID NO: 89 and corresponds to amino acids 24-144 of SEQ ID NO: 99 and the VL comprises an amino acid sequence of SEQ ID NO: 90 and corresponds to amino acids 160-266 of SEQ ID NO: 99
  • the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 271-325 of SEQ ID NO: 99
  • the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 326-353 of SEQ ID NO: 99
  • the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 354-395 of SEQ ID NO: 99
  • the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 396-507 of SEQ ID NO: 99
  • the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 99
  • the VH comprises an amino acid sequence of SEQ ID NO: 89 and corresponds to amino acids 24-144 of SEQ ID NO: 99 and the VL comprises an amino acid sequence of SEQ ID NO: 90 and corresponds to amino acids 160-266 of SEQ ID NO: 99
  • the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 271-325 of SEQ ID NO: 99
  • the transmembrane domain of the -155- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 326-353 of SEQ ID NO: 99
  • the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 354-395 of SEQ ID NO: 99
  • the signaling domain of the CAR comprises an amino acid sequence that is
  • the CAR comprises an amino acid sequence of SEQ ID NO: 99
  • the VH comprises an amino acid sequence of SEQ ID NO: 89 and corresponds to amino acids 24-144 of SEQ ID NO: 99 and the VL comprises an amino acid sequence of SEQ ID NO: 90 and corresponds to amino acids 160-266 of SEQ ID NO: 99
  • the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 271-325 of SEQ ID NO: 99
  • the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 326-353 of SEQ ID NO: 99
  • the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 354- 395 of SEQ ID NO: 99
  • the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 396-507 of SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 105: MALPVTALLLPLALLLHAARPGSAIQLTQSPSSLSASVGDRVTITCRASQGI SSALAWYQQKPGKAPKLLIYDASSLESGVPSRFSGSGSGTDFTLTISSLQPE DFATYYCQQFNSYPYTFGQGTKLEIKGGGGSGGGGSGGGGSEVQLVQSGAEV KKPGESLKISCKGSGYSFSSSWIGWVRQMPGKGLEWMGIIYPDDSDTRYSPS FQGQVTISADKSIRTAYLQWSSLKASDTAMYYCARHVTMIWGVIIDFWGQGT LVTVSSSGLDFVPVFLPAKPTTTPAPRPPTPAPTIASQPLS
  • the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 105. In some embodiments, the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 105. In some embodiments, the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 105. In some embodiments, the CAR comprises an amino acid sequence of SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 105, wherein the antigen binding domain of the CAR corresponds to amino acids 24-266 of SEQ ID NO: 105. In some embodiments, the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 105, wherein the antigen binding domain of the CAR corresponds to amino acids 24-266 of SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 105, wherein the antigen binding domain of the CAR corresponds to amino acids 24-266 of SEQ ID NO: 105. In some embodiments, the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 105, wherein the antigen binding domain of the CAR corresponds to amino acids 24- 266 of SEQ ID NO: 105. In some embodiments, the CAR comprises an amino acid sequence of SEQ ID NO: 105, wherein the antigen binding domain of the CAR corresponds to amino acids 24-266 of SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 105, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VL corresponds to amino acids 24-130 of SEQ ID NO: 105 and the VH corresponds to amino acids 146-266 of SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 105, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VL corresponds to amino acids 24-130 of SEQ ID NO: 105 and the VH corresponds to amino acids 146-266 of SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 105, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VL corresponds to amino acids 24-130 of SEQ ID NO: 105 and the VH corresponds to amino acids 146-266 of SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 105, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VL corresponds to amino acids 24-130 of SEQ ID NO: 105 and the VH corresponds to amino acids 146-266 of SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence of SEQ ID NO: 105, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VL corresponds to amino acids 24-130 of SEQ ID NO: 105 and the VH corresponds to amino acids 146-266 of SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 105, wherein the antigen binding domain of the CAR corresponds to amino acids 24-266 of SEQ ID NO: 105, a hinge domain of the CAR corresponds to amino acids 271-325 of SEQ ID NO: 105, a transmembrane domain of the CAR corresponds to amino acids 326-353 of SEQ ID NO: 105, a costimulatory domain of the CAR corresponds to amino acids 354-395 of SEQ ID NO: 105, and a signaling domain of the CAR corresponds to amino acids 396-507 of SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 105, wherein the antigen binding domain of the CAR corresponds to amino acids 24-266 of SEQ ID NO: 105, a hinge domain of the CAR corresponds to amino acids 271-325 of SEQ ID NO: 105, a transmembrane domain of the CAR corresponds to amino acids 326-353 of SEQ ID NO: 105, a costimulatory domain of the CAR corresponds to amino acids 354-395 of SEQ ID NO: 105, and a signaling domain of the CAR corresponds to amino acids 396-507 of SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 105, wherein the antigen binding domain of the CAR corresponds to amino acids 24-266 of SEQ ID NO: 105, a hinge domain of the CAR corresponds to amino acids 271-325 of SEQ ID NO: 105, a transmembrane domain of the CAR corresponds to amino acids 326-353 of SEQ ID NO: 105, a costimulatory domain of the CAR corresponds to amino acids 354-395 of SEQ ID NO: 105, and a signaling domain of the CAR corresponds to amino acids 396-507 of SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 105, wherein the antigen binding domain of the CAR corresponds to amino acids 24-266 of SEQ ID NO: 105, a hinge domain of the CAR corresponds to amino acids 271-325 of SEQ ID NO: 105, a transmembrane domain of the CAR corresponds to amino acids 326-353 of SEQ ID NO: 105, a costimulatory domain of the CAR corresponds to amino acids 354-395 of SEQ ID NO: 105, and a signaling domain of the CAR corresponds to amino acids 396-507 of SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence of SEQ ID NO: 105, wherein the antigen binding domain of the CAR corresponds to amino acids 24-266 of SEQ ID NO: 105, the hinge domain of the CAR corresponds to amino acids 271-325 of SEQ ID NO: 105, the transmembrane domain of the CAR corresponds to amino acids 326-353 of SEQ ID NO: 105, the costimulatory domain of the CAR corresponds to amino acids 354-395 of SEQ ID NO: 105, and the signaling domain of the CAR corresponds to amino acids 396- 507 of SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 105, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VL corresponds to amino acids 24-130 of SEQ ID NO: 105 and the VH corresponds to amino acids 146-266 of SEQ ID NO: 105, a hinge domain of the CAR corresponds to amino acids 271-325 of SEQ ID NO: 105, a transmembrane domain of the CAR corresponds to amino acids 326-353 of SEQ ID NO: 105, a costimulatory domain of the CAR corresponds to amino acids 354-395 of SEQ ID NO: 105, and a signaling domain of
  • the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 105, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VL corresponds to amino acids 24-130 of SEQ ID NO: 105 and the VH corresponds to amino acids 146-266 of SEQ ID NO: 105, a hinge domain of the CAR corresponds to amino acids 271-325 of SEQ ID NO: 105, a transmembrane domain of the CAR corresponds to amino acids 326-353 of SEQ ID NO: 105, a costimulatory domain of the CAR corresponds to amino acids 354-395 of SEQ ID NO: 105, and a signaling domain of the CAR corresponds to amino acids 396-507 of SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 105, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VL corresponds to amino acids 24-130 of SEQ ID NO: 105 and the VH corresponds to amino acids 146-266 of SEQ ID NO: 105, a hinge domain of the CAR corresponds to amino acids 271-325 of SEQ ID NO: 105, a transmembrane domain of the CAR corresponds to amino acids 326-353 of SEQ ID NO: 105, a costimulatory domain of the CAR corresponds to amino acids 354-395 of SEQ ID NO: 105, and a signaling domain of the CAR corresponds to amino acids 396-507 of SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 105, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VL corresponds to amino acids 24-130 of SEQ ID NO: 105 and the VH corresponds to amino acids 146-266 of SEQ ID NO: 105, a hinge domain of the CAR corresponds to amino acids 271-325 of SEQ ID NO: 105, a transmembrane domain of the CAR corresponds to amino acids 326-353 of SEQ ID NO: 105, a costimulatory domain of the CAR corresponds to amino acids 354-395 of SEQ ID NO: 105, and a signaling domain of the CAR corresponds to amino acids 396-507 of SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence of SEQ ID NO: 105, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VL corresponds to amino acids 24-130 of -159- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT SEQ ID NO: 105 and the VH corresponds to amino acids 146-266 of SEQ ID NO: 105, the hinge domain of the CAR corresponds to amino acids 271-325 of SEQ ID NO: 105, the transmembrane domain of the CAR corresponds to amino acids 326-353 of SEQ ID NO: 105, the costimulatory domain of the CAR corresponds to amino acids 354-395 of SEQ ID NO: 105, and the signaling domain of the CAR corresponds to amino acids 396-507 of SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 105, wherein the antigen binding domain of the CAR comprises an amino acid sequence of SEQ ID NO: 93 and corresponds to amino acids 24-266 of SEQ ID NO: 105, a hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 271-325 of SEQ ID NO: 105, a transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 326-353 of SEQ ID NO: 105, a costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 354-395 of SEQ ID NO: 105, and a signaling domain of the CAR comprises an
  • the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 105, wherein the antigen binding domain of the CAR comprises an amino acid sequence of SEQ ID NO: 93 and corresponds to amino acids 24-266 of SEQ ID NO: 105, a hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 271-325 of SEQ ID NO: 105, a transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 326-353 of SEQ ID NO: 105, a costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 354-395 of SEQ ID NO: 105, and a signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 396-507 of SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 105, wherein the antigen binding domain of the CAR comprises an amino acid sequence of SEQ ID NO: 93 and corresponds to amino acids 24-266 of SEQ ID NO: 105, the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 271-325 of SEQ ID NO: 105, the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 326-353 of SEQ ID NO: 105, the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and -160- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT corresponds to amino acids 354-395 of SEQ ID NO: 105, and the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 396- 507 of
  • the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 105, wherein the antigen binding domain of the CAR comprises an amino acid sequence of SEQ ID NO: 93 and corresponds to amino acids 24-266 of SEQ ID NO: 105, the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 271-325 of SEQ ID NO: 105, the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 326-353 of SEQ ID NO: 105, the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 354-395 of SEQ ID NO: 105, and the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 396-507 of SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence of SEQ ID NO: 105
  • the antigen binding domain of the CAR comprises an amino acid sequence of SEQ ID NO: 93 and corresponds to amino acids 24-266 of SEQ ID NO: 105
  • the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 271-325 of SEQ ID NO: 105
  • the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 326-353 of SEQ ID NO: 105
  • the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 354-395 of SEQ ID NO: 105
  • the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 396- 507 of SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 105, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VL comprises an amino acid sequence of SEQ ID NO: 90 and corresponds to amino acids 24-130 of SEQ ID NO: 105 and the VH comprises an amino acid sequence of SEQ ID NO: 89 and corresponds to amino acids 146-266 of SEQ ID NO: 105, a hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 271-325 of SEQ ID NO: 105, a transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 326-353 of SEQ ID NO: 105, a costimulatory
  • the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 105
  • the VL comprises an amino acid sequence of SEQ ID NO: 90 and corresponds to amino acids 24-130 of SEQ ID NO: 105
  • the VH comprises an amino acid sequence of SEQ ID NO: 89 and corresponds to amino acids 146-266 of SEQ ID NO: 105
  • the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 271-325 of SEQ ID NO: 105
  • the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 326-353 of SEQ ID NO: 105
  • the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 354-395 of SEQ ID NO: 105
  • the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 396- 507 of
  • the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 105
  • the VL comprises an amino acid sequence of SEQ ID NO: 90 and corresponds to amino acids 24-130 of SEQ ID NO: 105
  • the VH comprises an amino acid sequence of SEQ ID NO: 89 and corresponds to amino acids 146-266 of SEQ ID NO: 105
  • the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 271-325 of SEQ ID NO: 105
  • the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 326-353 of SEQ ID NO: 105
  • the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 354-395 of SEQ ID NO: 105
  • the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 396-507 of
  • the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 105
  • the VL comprises an amino acid sequence of SEQ ID NO: 90 and corresponds to amino acids 24-130 of SEQ ID NO: 105
  • the VH comprises an amino acid sequence of SEQ ID NO: 89 and corresponds to amino acids 146-266 of SEQ ID NO: 105
  • the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 271-325 of SEQ ID NO: 105
  • the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 326-353 of SEQ ID NO: 105
  • the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 354-395 of SEQ ID NO: 105
  • the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 396-507 of
  • the CAR comprises an amino acid sequence of SEQ ID NO: 105
  • the VL comprises an -162- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT amino acid sequence of SEQ ID NO: 90 and corresponds to amino acids 24-130 of SEQ ID NO: 105
  • the VH comprises an amino acid sequence of SEQ ID NO: 89 and corresponds to amino acids 146-266 of SEQ ID NO: 105
  • the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 271-325 of SEQ ID NO: 105
  • the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 326-353 of SEQ ID NO: 105
  • the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 354-395 of SEQ ID NO: 105
  • the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO:
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 106: MALPVTALLLPLALLLHAARPGSQVQLVQSGAEVKKPGSSVKVSCKDSGGTF SSYAISWVRQAPGQGLEWMGGIIPIFGTTNYAQQFQGRVTITADESTSTAYM ELSSLRSEDTAVYYCAREAVAADWLDPWGQGTLVTVSSGGGGSGGGGSGGGG SEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYG ASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSRFTFGPGT KVDIKSGLDFVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRP
  • the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 106. In some embodiments, the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 106. In some embodiments, the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 106. In some embodiments, the CAR comprises an amino acid sequence of SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 106, wherein the antigen binding domain of the CAR corresponds to amino acids 24-265 of SEQ ID NO: 106. In some embodiments, the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 106, wherein the antigen binding domain of the CAR corresponds to amino acids 24-265 of -163- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 106, wherein the antigen binding domain of the CAR corresponds to amino acids 24-265 of SEQ ID NO: 106. In some embodiments, the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 106, wherein the antigen binding domain of the CAR corresponds to amino acids 24- 265 of SEQ ID NO: 106. In some embodiments, the CAR comprises an amino acid sequence of SEQ ID NO: 106, wherein the antigen binding domain of the CAR corresponds to amino acids 24-265 of SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 106, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VH corresponds to amino acids 24-142 of SEQ ID NO: 106 and the VL corresponds to amino acids 158-265 of SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 106, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VH corresponds to amino acids 24-142 of SEQ ID NO: 106 and the VL corresponds to amino acids 158-265 of SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 106, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VH corresponds to amino acids 24-142 of SEQ ID NO: 106 and the VL corresponds to amino acids 158-265 of SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 106, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VH corresponds to amino acids 24-142 of SEQ ID NO: 106 and the VL corresponds to amino acids 158-265 of SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence of SEQ ID NO: 106, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VH corresponds to amino acids 24-142 of SEQ ID NO: 106 and the VL corresponds to amino acids 158-265 of SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 106, wherein the antigen binding domain of the CAR corresponds to amino acids 24-265 of SEQ ID NO: 106, a hinge domain of the CAR corresponds to amino acids 270-324 of SEQ ID NO: 106, a transmembrane domain of the CAR corresponds to amino acids 325-352 of SEQ ID NO: 106, a costimulatory domain of the CAR -164- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT corresponds to amino acids 353-394 of SEQ ID NO: 106, and a signaling domain of the CAR corresponds to amino acids 395-506 of SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 106, wherein the antigen binding domain of the CAR corresponds to amino acids 24-265 of SEQ ID NO: 106, the hinge domain of the CAR corresponds to amino acids 270-324 of SEQ ID NO: 106, the transmembrane domain of the CAR corresponds to amino acids 325-352 of SEQ ID NO: 106, the costimulatory domain of the CAR corresponds to amino acids 353-394 of SEQ ID NO: 106, and the signaling domain of the CAR corresponds to amino acids 395- 506 of SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 106, wherein the antigen binding domain of the CAR corresponds to amino acids 24-265 of SEQ ID NO: 106, the hinge domain of the CAR corresponds to amino acids 270-324 of SEQ ID NO: 106, the transmembrane domain of the CAR corresponds to amino acids 325-352 of SEQ ID NO: 106, the costimulatory domain of the CAR corresponds to amino acids 353-394 of SEQ ID NO: 106, and the signaling domain of the CAR corresponds to amino acids 395-506 of SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 106, wherein the antigen binding domain of the CAR corresponds to amino acids 24-265 of SEQ ID NO: 106, the hinge domain of the CAR corresponds to amino acids 270-324 of SEQ ID NO: 106, the transmembrane domain of the CAR corresponds to amino acids 325-352 of SEQ ID NO: 106, the costimulatory domain of the CAR corresponds to amino acids 353-394 of SEQ ID NO: 106, and the signaling domain of the CAR corresponds to amino acids 395-506 of SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence of SEQ ID NO: 106, wherein the antigen binding domain of the CAR corresponds to amino acids 24-265 of SEQ ID NO: 106, the hinge domain of the CAR corresponds to amino acids 270-324 of SEQ ID NO: 106, the transmembrane domain of the CAR corresponds to amino acids 325-352 of SEQ ID NO: 106, the costimulatory domain of the CAR corresponds to amino acids 353-394 of SEQ ID NO: 106, and the signaling domain of the CAR corresponds to amino acids 395-506 of SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 106, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VH corresponds to amino acids 24-142 of SEQ ID NO: 106 and the VL corresponds to amino acids 158-265 of SEQ ID NO: 106, a hinge domain of the CAR corresponds to amino acids 270-324 of SEQ ID NO: 106, a transmembrane domain -165- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT of the CAR corresponds to amino acids 325-352 of SEQ ID NO: 106, a costimulatory domain of the CAR corresponds to amino acids 353-394 of SEQ ID NO: 106, and a signal
  • the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 106, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VH corresponds to amino acids 24-142 of SEQ ID NO: 106 and the VL corresponds to amino acids 158-265 of SEQ ID NO: 106, the hinge domain of the CAR corresponds to amino acids 270-324 of SEQ ID NO: 106, the transmembrane domain of the CAR corresponds to amino acids 325-352 of SEQ ID NO: 106, the costimulatory domain of the CAR corresponds to amino acids 353-394 of SEQ ID NO: 106, and the signaling domain of the CAR corresponds to amino acids 395-506 of SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 106, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VH corresponds to amino acids 24-142 of SEQ ID NO: 106 and the VL corresponds to amino acids 158-265 of SEQ ID NO: 106, the hinge domain of the CAR corresponds to amino acids 270-324 of SEQ ID NO: 106, the transmembrane domain of the CAR corresponds to amino acids 325-352 of SEQ ID NO: 106, the costimulatory domain of the CAR corresponds to amino acids 353-394 of SEQ ID NO: 106, and the signaling domain of the CAR corresponds to amino acids 395- 506 of SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 106, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VH corresponds to amino acids 24- 142 of SEQ ID NO: 106 and the VL corresponds to amino acids 158-265 of SEQ ID NO: 106, the hinge domain of the CAR corresponds to amino acids 270-324 of SEQ ID NO: 106, the transmembrane domain of the CAR corresponds to amino acids 325-352 of SEQ ID NO: 106, the costimulatory domain of the CAR corresponds to amino acids 353-394 of SEQ ID NO: 106, and the signaling domain of the CAR corresponds to amino acids 395-506 of SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence of SEQ ID NO: 106, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VH corresponds to amino acids 24-142 of SEQ ID NO: 106 and the VL corresponds to amino acids 158-265 of SEQ ID NO: 106, the hinge domain of the CAR corresponds to amino acids 270-324 of SEQ ID NO: 106, the transmembrane domain of the CAR corresponds to amino acids 325-352 of SEQ ID NO: 106, the costimulatory domain of the CAR corresponds to amino acids 353-394 of SEQ -166- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT ID NO: 106, and the signaling domain of the CAR corresponds to amino acids 395-506 of SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 106, wherein the antigen binding domain of the CAR comprises an amino acid sequence of SEQ ID NO: 96 and corresponds to amino acids 24-265 of SEQ ID NO: 106, a hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 270-324 of SEQ ID NO: 106, a transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 325-352 of SEQ ID NO: 106, a costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 353-394 of SEQ ID NO: 106, and a signaling domain of the CAR
  • the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 106, wherein the antigen binding domain of the CAR comprises an amino acid sequence of SEQ ID NO: 96 and corresponds to amino acids 24-265 of SEQ ID NO: 106, the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 270-324 of SEQ ID NO: 106, the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 325-352 of SEQ ID NO: 106, the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 353-394 of SEQ ID NO: 106, and the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 395-506 of SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 106, wherein the antigen binding domain of the CAR comprises an amino acid sequence of SEQ ID NO: 96 and corresponds to amino acids 24-265 of SEQ ID NO: 106, the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 270-324 of SEQ ID NO: 106, the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 325-352 of SEQ ID NO: 106, the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 353-394 of SEQ ID NO: 106, and the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 395-506 of SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 106, wherein the antigen -167- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT binding domain of the CAR comprises an amino acid sequence of SEQ ID NO: 96 and corresponds to amino acids 24-265 of SEQ ID NO: 106, the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 270-324 of SEQ ID NO: 106, the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 325-352 of SEQ ID NO: 106, the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 353-394 of SEQ ID NO: 106, and the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 395- 50,
  • the CAR comprises an amino acid sequence of SEQ ID NO: 106
  • the antigen binding domain of the CAR comprises an amino acid sequence of SEQ ID NO: 96 and corresponds to amino acids 24-265 of SEQ ID NO: 106
  • the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 270-324 of SEQ ID NO: 106
  • the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 325-352 of SEQ ID NO: 106
  • the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 353-394 of SEQ ID NO: 106
  • the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 395-506 of SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 106, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VH comprises an amino acid sequence of SEQ ID NO: 94 and corresponds to amino acids 24-142 of SEQ ID NO: 106 and the VL comprises an amino acid sequence of SEQ ID NO: 95 and corresponds to amino acids 158-265 of SEQ ID NO: 106, a hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 270-324 of SEQ ID NO: 106, a transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 325-352 of SEQ ID NO: 106, a cost
  • the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 106, wherein the VH comprises an amino acid sequence of SEQ ID NO: 94 and corresponds to amino acids 24-142 of SEQ ID NO: 106 and the VL comprises an amino acid sequence of SEQ ID NO: 95 -168- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT and corresponds to amino acids 158-265 of SEQ ID NO: 106, the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 270-324 of SEQ ID NO: 106, the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 325-352 of SEQ ID NO: 106, the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 353-394 of SEQ ID NO: 106, and the signaling domain of
  • the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 106, wherein the VH comprises an amino acid sequence of SEQ ID NO: 94 and corresponds to amino acids 24-142 of SEQ ID NO: 106 and the VL comprises an amino acid sequence of SEQ ID NO: 95 and corresponds to amino acids 158-265 of SEQ ID NO: 106, the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 270-324 of SEQ ID NO: 106, the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 325-352 of SEQ ID NO: 106, the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 353-394 of SEQ ID NO: 106, and the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 395
  • the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 106, wherein the VH comprises an amino acid sequence of SEQ ID NO: 94 and corresponds to amino acids 24-142 of SEQ ID NO: 106 and the VL comprises an amino acid sequence of SEQ ID NO: 95 and corresponds to amino acids 158-265 of SEQ ID NO: 106, the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 270-324 of SEQ ID NO: 106, the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 325-352 of SEQ ID NO: 106, the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 353-394 of SEQ ID NO: 106, and the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 395
  • the CAR comprises an amino acid sequence of SEQ ID NO: 106
  • the VH comprises an amino acid sequence of SEQ ID NO: 94 and corresponds to amino acids 24-142 of SEQ ID NO: 106 and the VL comprises an amino acid sequence of SEQ ID NO: 95 and corresponds to amino acids 158-265 of SEQ ID NO: 106
  • the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 270-324 of SEQ ID NO: 106, -169- IPTS/128579164.3
  • the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 325-352 of SEQ ID NO: 106
  • the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 353-394 of SEQ ID NO: 106
  • the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 106
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 107: MALPVTALLLPLALLLHAARPGSEIVLTQSPGTLSLSPGERATLSCRASQSV SSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEP EDFAVYYCQQYGSSRFTFGPGTKVDIKGGGGSGGGGSGGGGSQVQLVQSGAE VKKPGSSVKVSCKDSGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTTNYAQ QFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREAVAADWLDPWGQGTL VTVSSSGLDFVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGG
  • the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 107. In some embodiments, the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 107. In some embodiments, the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 107. In some embodiments, the CAR comprises an amino acid sequence of SEQ ID NO: 107.
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 107, wherein the antigen binding domain of the CAR corresponds to amino acids 24-265 of SEQ ID NO: 107. In some embodiments, the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 107, wherein the antigen binding domain of the CAR corresponds to amino acids 24-265 of SEQ ID NO: 107.
  • the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 107, wherein the antigen binding domain of the CAR corresponds to amino acids 24-265 of SEQ ID NO: 107. In some embodiments, the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ -170- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT ID NO: 107, wherein the antigen binding domain of the CAR corresponds to amino acids 24- 265 of SEQ ID NO: 107.
  • the CAR comprises an amino acid sequence of SEQ ID NO: 107, wherein the antigen binding domain of the CAR corresponds to amino acids 24-265 of SEQ ID NO: 107.
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 107, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VL corresponds to amino acids 24-131 of SEQ ID NO: 107 and the VH corresponds to amino acids 147-265 of SEQ ID NO: 107.
  • the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 107, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VL corresponds to amino acids 24-131 of SEQ ID NO: 107 and the VH corresponds to amino acids 147-265 of SEQ ID NO: 107.
  • the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 107, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VL corresponds to amino acids 24-131 of SEQ ID NO: 107 and the VH corresponds to amino acids 147-265 of SEQ ID NO: 107.
  • the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 107, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VL corresponds to amino acids 24-131 of SEQ ID NO: 107 and the VH corresponds to amino acids 147-265 of SEQ ID NO: 107.
  • the CAR comprises an amino acid sequence of SEQ ID NO: 107, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VL corresponds to amino acids 24-131 of SEQ ID NO: 107 and the VH corresponds to amino acids 147-265 of SEQ ID NO: 107.
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 107, wherein the antigen binding domain of the CAR corresponds to amino acids 24-265 of SEQ ID NO: 107, a hinge domain of the CAR corresponds to amino acids 270-324 of SEQ ID NO: 107, a transmembrane domain of the CAR corresponds to amino acids 325-352 of SEQ ID NO: 107, a costimulatory domain of the CAR corresponds to amino acids 353-394 of SEQ ID NO: 107, and a signaling domain of the CAR corresponds to amino acids 395-506 of SEQ ID NO: 107.
  • the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 107, wherein the antigen binding domain of the CAR corresponds to amino acids 24-265 of -171- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT SEQ ID NO: 107, the hinge domain of the CAR corresponds to amino acids 270-324 of SEQ ID NO: 107, the transmembrane domain of the CAR corresponds to amino acids 325-352 of SEQ ID NO: 107, the costimulatory domain of the CAR corresponds to amino acids 353-394 of SEQ ID NO: 107, and the signaling domain of the CAR corresponds to amino acids 395- 506 of SEQ ID NO: 107.
  • the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 107, wherein the antigen binding domain of the CAR corresponds to amino acids 24-265 of SEQ ID NO: 107, the hinge domain of the CAR corresponds to amino acids 270-324 of SEQ ID NO: 107, the transmembrane domain of the CAR corresponds to amino acids 325-352 of SEQ ID NO: 107, the costimulatory domain of the CAR corresponds to amino acids 353-394 of SEQ ID NO: 107, and the signaling domain of the CAR corresponds to amino acids 395-506 of SEQ ID NO: 107.
  • the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 107, wherein the antigen binding domain of the CAR corresponds to amino acids 24-265 of SEQ ID NO: 107, the hinge domain of the CAR corresponds to amino acids 270-324 of SEQ ID NO: 107, the transmembrane domain of the CAR corresponds to amino acids 325-352 of SEQ ID NO: 107, the costimulatory domain of the CAR corresponds to amino acids 353-394 of SEQ ID NO: 107, and the signaling domain of the CAR corresponds to amino acids 395-506 of SEQ ID NO: 107.
  • the CAR comprises an amino acid sequence of SEQ ID NO: 107, wherein the antigen binding domain of the CAR corresponds to amino acids 24-265 of SEQ ID NO: 107, the hinge domain of the CAR corresponds to amino acids 270-324 of SEQ ID NO: 107, the transmembrane domain of the CAR corresponds to amino acids 325-352 of SEQ ID NO: 107, the costimulatory domain of the CAR corresponds to amino acids 353-394 of SEQ ID NO: 107, and the signaling domain of the CAR corresponds to amino acids 395-506 of SEQ ID NO: 107.
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 107, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VL corresponds to amino acids 24-131 of SEQ ID NO: 107 and the VH corresponds to amino acids 147-265 of SEQ ID NO: 107, a hinge domain of the CAR corresponds to amino acids 270-324 of SEQ ID NO: 107, a transmembrane domain of the CAR corresponds to amino acids 325-352 of SEQ ID NO: 107, a costimulatory domain of the CAR corresponds to amino acids 353-394 of SEQ ID NO: 107, and a signaling domain of the CAR corresponds to amino acids 395-506 of SEQ ID NO: 107.
  • the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ -172- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT ID NO: 107, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VL corresponds to amino acids 24-131 of SEQ ID NO: 107 and the VH corresponds to amino acids 147-265 of SEQ ID NO: 107, the hinge domain of the CAR corresponds to amino acids 270-324 of SEQ ID NO: 107, the transmembrane domain of the CAR corresponds to amino acids 325-352 of SEQ ID NO: 107, the costimulatory domain of the CAR corresponds to amino acids 353-394 of SEQ ID NO: 107, and the signaling domain of the CAR corresponds to amino acids 395-506 of SEQ ID NO: 107.
  • the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 107, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VL corresponds to amino acids 24-131 of SEQ ID NO: 107 and the V H corresponds to amino acids 147-265 of SEQ ID NO: 107, the hinge domain of the CAR corresponds to amino acids 270-324 of SEQ ID NO: 107, the transmembrane domain of the CAR corresponds to amino acids 325-352 of SEQ ID NO: 107, the costimulatory domain of the CAR corresponds to amino acids 353-394 of SEQ ID NO: 107, and the signaling domain of the CAR corresponds to amino acids 395- 506 of SEQ ID NO: 107.
  • the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 107, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VL corresponds to amino acids 24- 131 of SEQ ID NO: 107 and the VH corresponds to amino acids 147-265 of SEQ ID NO: 107, the hinge domain of the CAR corresponds to amino acids 270-324 of SEQ ID NO: 107, the transmembrane domain of the CAR corresponds to amino acids 325-352 of SEQ ID NO: 107, the costimulatory domain of the CAR corresponds to amino acids 353-394 of SEQ ID NO: 107, and the signaling domain of the CAR corresponds to amino acids 395-506 of SEQ ID NO: 107.
  • the CAR comprises an amino acid sequence of SEQ ID NO: 107, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VL corresponds to amino acids 24-131 of SEQ ID NO: 107 and the VH corresponds to amino acids 147-265 of SEQ ID NO: 107, the hinge domain of the CAR corresponds to amino acids 270- 324 of SEQ ID NO: 107, the transmembrane domain of the CAR corresponds to amino acids 325-352 of SEQ ID NO: 107, the costimulatory domain of the CAR corresponds to amino acids 353-394 of SEQ ID NO: 107, and the signaling domain of the CAR corresponds to amino acids 395-506 of SEQ ID NO: 107.
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 107, wherein the antigen binding domain of the CAR comprises an amino acid sequence of SEQ ID NO: 97 and corresponds to amino acids 24-265 -173- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT of SEQ ID NO: 107, a hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 270-324 of SEQ ID NO: 107, a transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 325-352 of SEQ ID NO: 107, a costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to
  • the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 107, wherein the antigen binding domain of the CAR comprises an amino acid sequence of SEQ ID NO: 97 and corresponds to amino acids 24-265 of SEQ ID NO: 107, the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 270-324 of SEQ ID NO: 107, the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 325-352 of SEQ ID NO: 107, the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 353-394 of SEQ ID NO: 107, and the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 395-506 of SEQ ID NO: 107.
  • the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 107, wherein the antigen binding domain of the CAR comprises an amino acid sequence of SEQ ID NO: 97 and corresponds to amino acids 24-265 of SEQ ID NO: 107, the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 270-324 of SEQ ID NO: 107, the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 325-352 of SEQ ID NO: 107, the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 353-394 of SEQ ID NO: 107, and the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 395-506 of SEQ ID NO: 107.
  • the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 107, wherein the antigen binding domain of the CAR comprises an amino acid sequence of SEQ ID NO: 97 and corresponds to amino acids 24-265 of SEQ ID NO: 107, the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 270-324 of SEQ ID NO: 107, the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 325-352 of SEQ ID NO: 107, the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and -174- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT corresponds to amino acids 353-394 of SEQ ID NO: 107, and the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 395- 50
  • the CAR comprises an amino acid sequence of SEQ ID NO: 107
  • the antigen binding domain of the CAR comprises an amino acid sequence of SEQ ID NO: 97 and corresponds to amino acids 24-265 of SEQ ID NO: 107
  • the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 270-324 of SEQ ID NO: 107
  • the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 325-352 of SEQ ID NO: 107
  • the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 353-394 of SEQ ID NO: 107
  • the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 395-506 of SEQ ID NO: 107.
  • the CAR comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 107, wherein the antigen binding domain of the CAR comprises a VH and a VL, wherein the VL comprises an amino acid sequence of SEQ ID NO: 95 and corresponds to amino acids 24-131 of SEQ ID NO: 107 and the VH comprises an amino acid sequence of SEQ ID NO: 94 and corresponds to amino acids 147-265 of SEQ ID NO: 107, a hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 270-324 of SEQ ID NO: 107, a transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 325-352 of SEQ ID NO: 107, a cost
  • the CAR comprises an amino acid sequence that is at least 90% identical to a sequence of SEQ ID NO: 107
  • the VL comprises an amino acid sequence of SEQ ID NO: 95 and corresponds to amino acids 24-131 of SEQ ID NO: 107 and the VH comprises an amino acid sequence of SEQ ID NO: 94 and corresponds to amino acids 147-265 of SEQ ID NO: 107
  • the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 270-324 of SEQ ID NO: 107
  • the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 325-352 of SEQ ID NO: 107
  • the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 353-394 of SEQ ID NO: 107
  • the CAR comprises an amino acid sequence that is at least 95% identical to a sequence of SEQ ID NO: 107, wherein the VL comprises an amino acid sequence of SEQ ID NO: 95 and corresponds to amino acids 24-131 of SEQ ID NO: 107 and the VH comprises an amino acid sequence of SEQ ID NO: 94 and corresponds to amino acids 147-265 of SEQ ID NO: 107, the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 270-324 of SEQ ID NO: 107, the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 325-352 of SEQ ID NO: 107, the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 353-394 of SEQ ID NO: 107, and the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 395
  • the CAR comprises an amino acid sequence that is at least 98% identical to a sequence of SEQ ID NO: 107
  • the VL comprises an amino acid sequence of SEQ ID NO: 95 and corresponds to amino acids 24-131 of SEQ ID NO: 107 and the VH comprises an amino acid sequence of SEQ ID NO: 94 and corresponds to amino acids 147-265 of SEQ ID NO: 107
  • the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 270-324 of SEQ ID NO: 107
  • the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 325-352 of SEQ ID NO: 107
  • the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 353-394 of SEQ ID NO: 107
  • the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 395
  • the CAR comprises an amino acid sequence of SEQ ID NO: 107
  • the VL comprises an amino acid sequence of SEQ ID NO: 95 and corresponds to amino acids 24-131 of SEQ ID NO: 107 and the VH comprises an amino acid sequence of SEQ ID NO: 94 and corresponds to amino acids 147-265 of SEQ ID NO: 107
  • the hinge domain of the CAR comprises an amino acid sequence of SEQ ID NO: 59 and corresponds to amino acids 270-324 of SEQ ID NO: 107
  • the transmembrane domain of the CAR comprises an amino acid sequence of SEQ ID NO: 61 and corresponds to amino acids 325-352 of SEQ ID NO: 107
  • the costimulatory domain of the CAR comprises an amino acid sequence of SEQ ID NO: 101 and corresponds to amino acids 353-394 of SEQ ID NO: 107
  • the signaling domain of the CAR comprises an amino acid sequence of SEQ ID NO: 102 and corresponds to amino acids 395-506 of SEQ ID NO: 107.
  • the antigen binding domain of the CAR may be directly fused to the hinge domain of the CAR.
  • the antigen binding domain of the CAR may be connected to the hinge domain of the CAR through a polypeptide linker, such as those provided for herein.
  • the polypeptide linker comprises an amino acid sequence of SGLD (SEQ ID NO: 100).
  • the polypeptide linker connects the C-terminus of the antigen binding domain to the N-terminus of the hinge region.
  • the antigen binding domain comprises a VH and a VL and the polypeptide linker connects the C-terminus of the VH to the N-terminus of the hinge region. In some embodiments, the antigen binding domain comprises a VH and a VL and the polypeptide linker connects the C-terminus of the V L to the N-terminus of the hinge region.
  • the pseudotyped viral particle further comprises a heterologous nucleic acid molecule encoding a cargo of interest.
  • the nucleic acid molecule may be useful for modulating the expression of a target gene.
  • the cargo can be used to modulate the activity of a cell or express a protein that is trafficked to the surface of the target cell. Therefore, in some embodiments, the nucleic acid may comprise an siRNA or an shRNA.
  • the nucleic acid may also encode for a cargo of interest. Therefore, in some embodiments, the cargo of interest may comprise a polypeptide or portion thereof, a protein or portion thereof, a chimeric antigen receptor or portion thereof, or a tumor antigen or a portion thereof.
  • the cargo of interest is an antibody that is produced by the virus, which can then be secreted by the cell that is infected with the virus.
  • the term “protein” can refer to any polypeptide that carries a native function in a cellular environment. Therefore, in some embodiments, the protein encoded by the nucleic acid cargo of interest may comprise an enzyme, a nuclear receptor, a transporter, a ribosomal protein, a membrane bound protein, a cytoplasmic protein, a G-protein coupled receptor, a voltage gated ion channel, a secretory protein, a mitochondria protein, a cytokine, a chimeric antigen receptor, a tumor antigen, or a portion or chimeric species thereof.
  • the viral particle comprising a heterologous viral glycoprotein as provided for herein and comprising a targeting moiety as provided for herein can be used to express the heterologous molecule of interest in the target cell.
  • the CAR can be expressed in a T cell that is targeted by a viral particle -177- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT pseudotyped with a VSV-G protein or a SVCV-G protein as provided for herein.
  • the viral particle can comprise a targeting moiety that binds to a target on the surface of a T cell, such as, but not limited to CD2, CD3, CD4, CD5, CD7 or CD8.
  • the target is CD2. In some embodiments, the target is CD3. In some embodiments, the target is CD4. In some embodiments, the target is CD5. In some embodiments, the target is CD6. In some embodiments, the target is CD7. In some embodiments, the target is CD8. In some embodiments, the targeting moiety targeting CD7 is as provided for herein. In some embodiments, the targeting moiety targeting CD8 is as provided for herein.
  • the pseudotyped viral particle is a recombinant lentivirus. In some embodiments, the recombinant pseudotyped viral particle is replication competent. In some embodiments, the recombinant pseudotyped viral particle is replication incompetent.
  • a viral particle comprising a heterologous viral glycoprotein and a targeting moiety comprising a polypeptide having a formula T-S1, wherein T is a target binding domain and S1 is a stalk portion
  • the heterologous viral glycoprotein comprises a sequence selected from SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 52, or SEQ ID NO: 53
  • the target binding domain comprises a sequence selected from SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 50, or SEQ ID NO: 51
  • the stalk portion S1 comprises a variant Fc protein comprising a sequence that is a variant of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28
  • the variant of SEQ ID NO: 26 comprises one or more mutations selected from the group consisting of L234A, L235A, N
  • the heterologous viral glycoprotein comprises a sequence of SEQ ID NO: 22. In some embodiments, the heterologous viral glycoprotein comprises a sequence of SEQ ID NO: 23. In some embodiments, the heterologous viral glycoprotein comprises a sequence of SEQ ID NO: 24. In some embodiments, the heterologous viral glycoprotein comprises a sequence of SEQ ID NO: 25. In some embodiments, the heterologous viral -178- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT glycoprotein comprises a sequence of SEQ ID NO: 52. In some embodiments, the heterologous viral glycoprotein comprises a sequence of SEQ ID NO: 53. In some embodiments, the targeting moiety comprises an amino acid sequence of SEQ ID NO: 38.
  • the targeting moiety comprises an amino acid sequence of SEQ ID NO: 39. In some embodiments, the targeting moiety comprises an amino acid sequence of SEQ ID NO: 50. In some embodiments, the targeting moiety comprises an amino acid sequence of SEQ ID NO: 51.
  • the variant Fc protein is a variant of SEQ ID NO: 26 and comprises one or more mutations selected from the group consisting of L234A, L235A, N297A, P329G, I253A, H310A, and H435A.
  • the variant Fc protein is a variant of SEQ ID NO: 27 and comprises one or more mutations selected from the group consisting of N297A, P329G, I253A, H310A, and H435A. In some embodiments, the variant Fc protein is a variant of SEQ ID NO: 28 and comprises one or more mutations selected from the group consisting of S228P, L235E, N297A, P329G, I253A, H310A, and H435A. In some embodiments, the transmembrane domain has an amino acid sequence of SEQ ID NO: 61. In some embodiments, the transmembrane domain has an amino acid sequence of SEQ ID NO: 62.
  • the viral particle further comprises a nucleic acid molecule encoding a heterologous molecule of interest.
  • the heterologous molecule of interest is as provided for herein.
  • the heterologous molecule of interest is a CAR as provided for herein.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 99, at least 90% identity to SEQ ID NO: 99, at least 95% identity to SEQ ID NO: 99. at least 99% identity to SEQ ID NO: 99, or at least 100% identity to SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 105, at least 90% identity to SEQ ID NO: 105, at least 95% identity to SEQ ID NO: 105. at least 99% identity to SEQ ID NO: 105, or at least 100% identity to SEQ ID NO: 105. In some embodiments, the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 106, at least 90% identity to SEQ ID NO: 106, at least 95% identity to SEQ ID NO: 106. at least 99% identity to SEQ ID NO: 106, or at least 100% identity to SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 107, at least 90% identity to SEQ ID NO: 107, at least 95% identity to SEQ ID NO: 107. at least 99% identity to SEQ ID NO: 107, or at least 100% identity to SEQ ID NO: 107.
  • a viral particle comprising a heterologous viral glycoprotein and a targeting moiety comprising a polypeptide having a formula T-S1, wherein T is a target binding domain and S1 is a stalk portion, wherein the -179- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT heterologous viral glycoprotein comprises a sequence selected from SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 52, or SEQ ID NO: 53; wherein the target binding domain comprises a sequence selected from SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 50, or SEQ ID NO: 51; wherein the stalk portion S1 comprises a formula of L1- Fc-L2-X1; wherein L1 is a linker comprising a sequence selected from SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO
  • SEQ ID NO: 73 SEQ ID NO: 74, SEQ ID NO: 75, or SEQ ID NO: 76, or is absent
  • X1 is a polypeptide comprising a transmembrane domain having a formula of ECD-TM-ICD, wherein ECD is an extracellular domain having a sequence of SEQ ID NO: 59, SEQ ID NO: 60, or any fragment thereof, or is absent
  • TM is a transmembrane domain having a sequence of SEQ ID NO: 61 or SEQ ID NO: 62 or any fragment thereof
  • ICD is an intracellular domain or protein that facilitates the incorporation of the targeting moiety into the envelope of the viral particle, wherein the ICD comprises an env incorporation motif comprising an amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64 or the ICD is absent.
  • the heterologous viral glycoprotein comprises a sequence of SEQ ID NO: 22. In some embodiments, the heterologous viral glycoprotein comprises a sequence of SEQ ID NO: 23. In some embodiments, the heterologous viral glycoprotein comprises a sequence of SEQ ID NO: 24. In some embodiments, the heterologous viral glycoprotein comprises a sequence of SEQ ID NO: 25. In some embodiments, the heterologous viral glycoprotein comprises a sequence of SEQ ID NO: 52. In some embodiments, the heterologous viral glycoprotein comprises a sequence of SEQ ID NO: 53. In some embodiments, T comprises an amino acid sequence of SEQ ID NO: 38. In some embodiments, T comprises an amino acid sequence of SEQ ID NO: 39.
  • T comprises an amino acid sequence of SEQ ID NO: 50. In some embodiments, T comprises an amino acid sequence of SEQ ID NO: 51. In some embodiments, L1 is absent. In some embodiments, L1 comprises an amino acid sequence of SEQ ID NO: 54. In some -180- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT embodiments, L1 comprises an amino acid sequence of SEQ ID NO: 55. In some embodiments, L1 comprises an amino acid sequence of SEQ ID NO: 56. In some embodiments, L1 comprises an amino acid sequence of SEQ ID NO: 57. In some embodiments, L1 comprises an amino acid sequence of SEQ ID NO: 58.
  • L1 comprises an amino acid sequence of SEQ ID NO: 73. In some embodiments, L1 comprises an amino acid sequence of SEQ ID NO: 74. In some embodiments, L1 comprises an amino acid sequence of SEQ ID NO: 75. In some embodiments, L1 comprises an amino acid sequence of SEQ ID NO: 76. In some embodiments, the variant Fc protein is a variant of SEQ ID NO: 26 and comprises one or more mutations selected from the group consisting of L234A, L235A, N297A, P329G, I253A, H310A, and H435A.
  • the variant Fc protein is a variant of SEQ ID NO: 27 and comprises one or more mutations selected from the group consisting of N297A, P329G, I253A, H310A, and H435A.
  • the variant Fc protein is a variant of SEQ ID NO: 28 and comprises one or more mutations selected from the group consisting of S228P, L235E, N297A, P329G, I253A, H310A, and H435A.
  • L2 is absent.
  • L2 comprises an amino acid sequence of SEQ ID NO: 54.
  • L2 comprises an amino acid sequence of SEQ ID NO: 55.
  • L2 comprises an amino acid sequence of SEQ ID NO: 56. In some embodiments, L2 comprises an amino acid sequence of SEQ ID NO: 57. In some embodiments, L2 comprises an amino acid sequence of SEQ ID NO: 58. In some embodiments, L2 comprises an amino acid sequence of SEQ ID NO: 73. In some embodiments, L2 comprises an amino acid sequence of SEQ ID NO: 74. In some embodiments, L2 comprises an amino acid sequence of SEQ ID NO: 75. In some embodiments, L2 comprises an amino acid sequence of SEQ ID NO: 76. In some embodiments, ECD is absent. In some embodiments, ECD comprises an amino acid sequence of SEQ ID NO: 59.
  • ECD comprises an amino acid sequence of SEQ ID NO: 60.
  • TM comprises an amino acid sequence of SEQ ID NO: 61.
  • TM comprises an amino acid sequence of SEQ ID NO: 62.
  • ICD is absent.
  • ICD is present and the env incorporation motif has an amino acid sequence of SEQ ID NO: 63.
  • ICD is present and the env incorporation motif has an amino acid sequence of SEQ ID NO: 64.
  • the viral particle further comprises a nucleic acid molecule encoding a heterologous molecule of interest.
  • the heterologous molecule of interest is as provided for herein.
  • the heterologous molecule of interest is a CAR as provided for herein.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 99, at least 90% identity to SEQ ID NO: -181- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT 99, at least 95% identity to SEQ ID NO: 99. at least 99% identity to SEQ ID NO: 99, or at least 100% identity to SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 105, at least 90% identity to SEQ ID NO: 105, at least 95% identity to SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 106, at least 90% identity to SEQ ID NO: 106, at least 95% identity to SEQ ID NO: 106. at least 99% identity to SEQ ID NO: 106, or at least 100% identity to SEQ ID NO: 106. In some embodiments, the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 107, at least 90% identity to SEQ ID NO: 107, at least 95% identity to SEQ ID NO: 107.
  • a viral particle comprising a heterologous viral glycoprotein and a targeting moiety comprising a polypeptide having a formula T-S1, wherein T is a target binding domain and S1 is a stalk portion, wherein the heterologous viral glycoprotein comprises a sequence selected from SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 52, or SEQ ID NO: 53; wherein the target binding domain comprises a sequence selected from SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 50, or SEQ ID NO: 51; wherein the stalk portion S1 comprises a formula of L1- Fc-L2-X1; wherein L1 is a linker comprising a sequence of SEQ ID NO: 55 or is absent; Fc is a variant Fc protein comprising a sequence that is a variant of SEQ ID NO:
  • the heterologous viral glycoprotein comprises a sequence of SEQ ID NO: 22. In some -182- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT embodiments, the heterologous viral glycoprotein comprises a sequence of SEQ ID NO: 23. In some embodiments, the heterologous viral glycoprotein comprises a sequence of SEQ ID NO: 24. In some embodiments, the heterologous viral glycoprotein comprises a sequence of SEQ ID NO: 25. In some embodiments, the heterologous viral glycoprotein comprises a sequence of SEQ ID NO: 52. In some embodiments, the heterologous viral glycoprotein comprises a sequence of SEQ ID NO: 53. In some embodiments, T comprises an amino acid sequence of SEQ ID NO: 38.
  • T comprises an amino acid sequence of SEQ ID NO: 39. In some embodiments, T comprises an amino acid sequence of SEQ ID NO: 50. In some embodiments, T comprises an amino acid sequence of SEQ ID NO: 51. In some embodiments, L1 is absent. In some embodiments, L1 comprises an amino acid sequence of SEQ ID NO: 55. In some embodiments, the variant Fc protein is a variant of SEQ ID NO: 26 and comprises one or more mutations selected from the group consisting of L234A, L235A, N297A, P329G, I253A, H310A, and H435A.
  • the variant Fc protein is a variant of SEQ ID NO: 27 and comprises one or more mutations selected from the group consisting of N297A, P329G, I253A, H310A, and H435A.
  • the variant Fc protein is a variant of SEQ ID NO: 28 and comprises one or more mutations selected from the group consisting of S228P, L235E, N297A, P329G, I253A, H310A, and H435A.
  • L2 is absent.
  • L2 comprises an amino acid sequence of SEQ ID NO: 55.
  • ECD is absent.
  • ECD comprises an amino acid sequence of SEQ ID NO: 60.
  • TM comprises an amino acid sequence of SEQ ID NO: 62.
  • ICD is absent.
  • ICD is present and the env incorporation motif has an amino acid sequence of SEQ ID NO: 63.
  • ICD is present and the env incorporation motif has an amino acid sequence of SEQ ID NO: 64.
  • the viral particle further comprises a nucleic acid molecule encoding a heterologous molecule of interest.
  • the heterologous molecule of interest is as provided for herein.
  • the heterologous molecule of interest is a CAR as provided for herein.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 99, at least 90% identity to SEQ ID NO: 99, at least 95% identity to SEQ ID NO: 99. at least 99% identity to SEQ ID NO: 99, or at least 100% identity to SEQ ID NO: 99. In some embodiments, the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 105, at least 90% identity to SEQ ID NO: 105, at least 95% identity to SEQ ID NO: 105. at least 99% identity to SEQ ID NO: 105, or at least 100% identity to SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence having at least 85% identity -183- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT to SEQ ID NO: 106, at least 90% identity to SEQ ID NO: 106, at least 95% identity to SEQ ID NO: 106. at least 99% identity to SEQ ID NO: 106, or at least 100% identity to SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 107, at least 90% identity to SEQ ID NO: 107, at least 95% identity to SEQ ID NO: 107. at least 99% identity to SEQ ID NO: 107, or at least 100% identity to SEQ ID NO: 107.
  • a viral particle comprising a heterologous viral glycoprotein and a targeting moiety comprising a polypeptide having a formula T-S1, wherein T is a target binding domain and S1 is a stalk portion, wherein the heterologous viral glycoprotein comprises a sequence of SEQ ID NO: 23 or SEQ ID NO: 25; wherein the target binding domain comprises a sequence of SEQ ID NO: 39; wherein the stalk portion S1 comprises a formula of L1-Fc-L2-X1; wherein L1 is a linker comprising a sequence of SEQ ID NO: 55; Fc is a variant Fc protein comprising a sequence fo SEQ ID NO: 104; L2 is a linker and is absent; and X1 is a polypeptide comprising a transmembrane domain having a formula of ECD-TM-ICD, wherein ECD is an extracellular domain having a sequence of SEQ ID NO: 60; TM is a transmembrane domain having
  • the viral particle further comprises a nucleic acid molecule encoding a heterologous molecule of interest.
  • the heterologous molecule of interest is as provided for herein.
  • the heterologous molecule of interest is a CAR as provided for herein.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 99, at least 90% identity to SEQ ID NO: 99, at least 95% identity to SEQ ID NO: 99. at least 99% identity to SEQ ID NO: 99, or at least 100% identity to SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 105, at least 90% identity to SEQ ID NO: 105, at least 95% identity to SEQ ID NO: 105. at least 99% identity to SEQ ID NO: 105, or at least 100% identity to SEQ ID NO: 105. In some embodiments, the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 106, at least 90% identity to SEQ ID NO: 106, at least 95% identity to SEQ ID NO: 106. at least 99% identity to SEQ ID NO: 106, or at least 100% identity to SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 107, at least 90% identity to SEQ ID NO: 107, at least 95% -184- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT identity to SEQ ID NO: 107. at least 99% identity to SEQ ID NO: 107, or at least 100% identity to SEQ ID NO: 107.
  • a viral particle comprising a heterologous viral glycoprotein and a targeting moiety
  • the heterologous viral glycoprotein comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 23 or SEQ ID NO: 25, having at least 95% identity to SEQ ID NO: 23 or SEQ ID NO: 25, having at least 99% identity to SEQ ID NO: 23 or SEQ ID NO: 25, or having at least 100% identity to SEQ ID NO: 23 or SEQ ID NO: 25
  • the targeting moiety comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 98, at least 95% identity to SEQ ID NO: 98, at least 99% identity to SEQ ID NO: 98, or at least 100% identity to SEQ ID NO: 98.
  • the viral particle further comprises a nucleic acid molecule encoding a heterologous molecule of interest.
  • the heterologous molecule of interest is as provided for herein.
  • the heterologous molecule of interest is a CAR as provided for herein.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 99, at least 90% identity to SEQ ID NO: 99, at least 95% identity to SEQ ID NO: 99. at least 99% identity to SEQ ID NO: 99, or at least 100% identity to SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 105, at least 90% identity to SEQ ID NO: 105, at least 95% identity to SEQ ID NO: 105. at least 99% identity to SEQ ID NO: 105, or at least 100% identity to SEQ ID NO: 105. In some embodiments, the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 106, at least 90% identity to SEQ ID NO: 106, at least 95% identity to SEQ ID NO: 106. at least 99% identity to SEQ ID NO: 106, or at least 100% identity to SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 107, at least 90% identity to SEQ ID NO: 107, at least 95% identity to SEQ ID NO: 107. at least 99% identity to SEQ ID NO: 107, or at least 100% identity to SEQ ID NO: 107.
  • a viral particle comprising a heterologous viral glycoprotein and a targeting moiety, wherein the heterologous viral glycoprotein comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 52 or SEQ ID NO: 53, having at least 95% identity to SEQ ID NO: 52 or SEQ ID NO: 53, having at least 99% identity to SEQ ID NO: 52 or SEQ ID NO: 53, or having at least 100% identity to SEQ ID NO: 52 or SEQ ID NO: 53; and the targeting moiety comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 98, at least 95% identity to SEQ ID NO: 98, at least 99% identity to SEQ ID NO: 98, or at least 100% identity to SEQ ID NO: 98.
  • the viral particle further comprises a nucleic acid molecule encoding a heterologous molecule of interest.
  • the heterologous molecule of interest is as provided for herein.
  • the heterologous molecule of interest is a CAR as provided for herein.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 99, at least 90% identity to SEQ ID NO: 99, at least 95% identity to SEQ ID NO: 99. at least 99% identity to SEQ ID NO: 99, or at least 100% identity to SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 105, at least 90% identity to SEQ ID NO: 105, at least 95% identity to SEQ ID NO: 105. at least 99% identity to SEQ ID NO: 105, or at least 100% identity to SEQ ID NO: 105. In some embodiments, the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 106, at least 90% identity to SEQ ID NO: 106, at least 95% identity to SEQ ID NO: 106. at least 99% identity to SEQ ID NO: 106, or at least 100% identity to SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 107, at least 90% identity to SEQ ID NO: 107, at least 95% identity to SEQ ID NO: 107. at least 99% identity to SEQ ID NO: 107, or at least 100% identity to SEQ ID NO: 107.
  • a viral particle comprising a targeting moiety comprising a flexible polypeptide
  • the viral particle comprising a heterologous viral structural protein and a targeting moiety, wherein the targeting moiety comprises a polypeptide having a formula of T-S1, wherein T is a target binding domain and S1 is a stalk portion; wherein the target binding domain comprises an amino acid sequence of SEQ ID NO: 38 or SEQ ID NO: 39; wherein the stalk portion S1 comprises a formula of L3- X1; wherein L3 is a flexible peptide linker having an amino acid sequence selected from SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, or SEQ ID NO: 58; and X1 is a polypeptide comprising a transmembrane domain having a formula ECD-TM-ICD, wherein ECD is an extracellular domain having an amino acid sequence of SEQ ID NO: 59 or SEQ ID NO: 60,
  • the target binding domain has an amino acid sequence of SEQ ID NO: 38. In some embodiments, the target binding domain has an amino acid sequence -186- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT of SEQ ID NO: 39.
  • L3 has an amino acid sequence of SEQ ID NO: 54. In some embodiments, L3 has an amino acid sequence of SEQ ID NO: 55. In some embodiments, L3 has an amino acid sequence of SEQ ID NO: 56. In some embodiments, L3 has an amino acid sequence of SEQ ID NO: 57. In some embodiments, L3 has an amino acid sequence of SEQ ID NO: 58.
  • the ECD has an amino acid sequence of SEQ ID NO: 59. In some embodiments, the ECD has an amino acid sequence of SEQ ID NO: 60. In some embodiments, the TM has an amino acid sequence of SEQ ID NO: 61. In some embodiments, the TM has an amino acid sequence of SEQ ID NO: 62. In some embodiments, the env incorporation motif has an amino acid sequence of SEQ ID NO: 63. In some embodiments, the env incorporation motif has an amino acid sequence of SEQ ID NO: 64. In some embodiments, the viral particle further comprises a nucleic acid molecule encoding a heterologous molecule of interest. In some embodiments, the heterologous molecule of interest is as provided for herein.
  • the heterologous molecule of interest is a CAR as provided for herein.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 99, at least 90% identity to SEQ ID NO: 99, at least 95% identity to SEQ ID NO: 99. at least 99% identity to SEQ ID NO: 99, or at least 100% identity to SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 105, at least 90% identity to SEQ ID NO: 105, at least 95% identity to SEQ ID NO: 105. at least 99% identity to SEQ ID NO: 105, or at least 100% identity to SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 106, at least 90% identity to SEQ ID NO: 106, at least 95% identity to SEQ ID NO: 106. at least 99% identity to SEQ ID NO: 106, or at least 100% identity to SEQ ID NO: 106. In some embodiments, the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 107, at least 90% identity to SEQ ID NO: 107, at least 95% identity to SEQ ID NO: 107. at least 99% identity to SEQ ID NO: 107, or at least 100% identity to SEQ ID NO: 107.
  • a viral particle comprising a heterologous viral structural protein and a targeting moiety, wherein the targeting moiety comprises a polypeptide having a formula of T-S1, wherein T is a target binding domain and S1 is a stalk portion; wherein the target binding domain comprises an amino acid sequence of SEQ ID NO: 50 or SEQ ID NO: 51; wherein the stalk portion S1 comprises a formula of L3- X1; wherein L3 is a flexible peptide linker having an amino acid sequence selected from SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, or SEQ ID NO: 58; and X1 is a polypeptide comprising a transmembrane domain having a formula ECD-TM-ICD, wherein -187- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT ECD is an extracellular domain having an amino acid sequence of SEQ ID NO: 59 or S
  • the target binding domain has an amino acid sequence of SEQ ID NO: 50. In some embodiments, the target binding domain has an amino acid sequence of SEQ ID NO: 51. In some embodiments, L3 has an amino acid sequence of SEQ ID NO: 54. In some embodiments, L3 has an amino acid sequence of SEQ ID NO: 55. In some embodiments, L3 has an amino acid sequence of SEQ ID NO: 56. In some embodiments, L3 has an amino acid sequence of SEQ ID NO: 57. In some embodiments, L3 has an amino acid sequence of SEQ ID NO: 58. In some embodiments, the ECD has an amino acid sequence of SEQ ID NO: 59. In some embodiments, the ECD has an amino acid sequence of SEQ ID NO: 60.
  • the TM has an amino acid sequence of SEQ ID NO: 61. In some embodiments, the TM has an amino acid sequence of SEQ ID NO: 62. In some embodiments, the env incorporation motif has an amino acid sequence of SEQ ID NO: 63. In some embodiments, the env incorporation motif has an amino acid sequence of SEQ ID NO: 64. In some embodiments, the viral particle further comprises a nucleic acid molecule encoding a heterologous molecule of interest. In some embodiments, the heterologous molecule of interest is as provided for herein. In some embodiments, the heterologous molecule of interest is a CAR as provided for herein.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 99, at least 90% identity to SEQ ID NO: 99, at least 95% identity to SEQ ID NO: 99. at least 99% identity to SEQ ID NO: 99, or at least 100% identity to SEQ ID NO: 99. In some embodiments, the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 105, at least 90% identity to SEQ ID NO: 105, at least 95% identity to SEQ ID NO: 105. at least 99% identity to SEQ ID NO: 105, or at least 100% identity to SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 106, at least 90% identity to SEQ ID NO: 106, at least 95% identity to SEQ ID NO: 106. at least 99% identity to SEQ ID NO: 106, or at least 100% identity to SEQ ID NO: 106. In some embodiments, the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 107, at least 90% identity to SEQ ID NO: 107, at least 95% identity to SEQ ID NO: 107. at least 99% identity to SEQ ID NO: 107, or at least 100% identity to SEQ ID NO: 107.
  • a viral particle comprising a heterologous viral structural protein and a targeting moiety, wherein the targeting moiety comprises a polypeptide having a formula of T-S1, wherein the heterologous viral structural protein comprises a sequence of SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 52, or SEQ ID NO: 53; wherein T is a target binding domain and S1 is a stalk portion, wherein the target binding domain comprises an amino acid sequence of SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 50, or SEQ ID NO: 51; wherein the stalk portion S1 comprises a formula of L3-X1; wherein L3 is a flexible peptide linker having an amino acid sequence selected from SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO:
  • the heterologous viral structural protein comprises a sequence of SEQ ID NO: 22. In some embodiments, the heterologous viral structural protein comprises a sequence of SEQ ID NO: 23. In some embodiments, the heterologous viral structural protein comprises a sequence of SEQ ID NO: 24. In some embodiments, the heterologous viral structural protein comprises a sequence of SEQ ID NO: 25. In some embodiments, the heterologous viral structural protein comprises a sequence of SEQ ID NO: 52. In some embodiments, the heterologous viral structural protein comprises a sequence of SEQ ID NO: 53. In some embodiments, the target binding domain has an amino acid sequence of SEQ ID NO: 38. In some embodiments, the target binding domain has an amino acid sequence of SEQ ID NO: 39.
  • the target binding domain has an amino acid sequence of SEQ ID NO: 50. In some embodiments, the target binding domain has an amino acid sequence of SEQ ID NO: 51. In some embodiments, L3 has an amino acid sequence of SEQ ID NO: 54. In some embodiments, L3 has an amino acid sequence of SEQ ID NO: 55. In some embodiments, L3 has an amino acid sequence of SEQ ID NO: 56. In some embodiments, L3 has an amino acid sequence of SEQ ID NO: 57. In some embodiments, L3 has an amino acid sequence of SEQ ID NO: 58. In some embodiments, the ECD has an amino acid sequence of SEQ ID NO: 59. In some embodiments, the ECD has an amino acid sequence of SEQ ID NO: 60.
  • the TM has -189- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT an amino acid sequence of SEQ ID NO: 61.
  • the TM has an amino acid sequence of SEQ ID NO: 62.
  • the env incorporation motif has an amino acid sequence of SEQ ID NO: 63.
  • the env incorporation motif has an amino acid sequence of SEQ ID NO: 64.
  • the viral particle further comprises a nucleic acid molecule encoding a heterologous molecule of interest.
  • the heterologous molecule of interest is as provided for herein.
  • the heterologous molecule of interest is a CAR as provided for herein.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 99, at least 90% identity to SEQ ID NO: 99, at least 95% identity to SEQ ID NO: 99. At least 99% identity to SEQ ID NO: 99, or at least 100% identity to SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 105, at least 90% identity to SEQ ID NO: 105, at least 95% identity to SEQ ID NO: 105. at least 99% identity to SEQ ID NO: 105, or at least 100% identity to SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 106, at least 90% identity to SEQ ID NO: 106, at least 95% identity to SEQ ID NO: 106. at least 99% identity to SEQ ID NO: 106, or at least 100% identity to SEQ ID NO: 106. In some embodiments, the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 107, at least 90% identity to SEQ ID NO: 107, at least 95% identity to SEQ ID NO: 107. at least 99% identity to SEQ ID NO: 107, or at least 100% identity to SEQ ID NO: 107.
  • a viral particle comprising a heterologous viral structural protein and a targeting moiety, wherein the targeting moiety comprises a polypeptide having a formula of T-S1, wherein the heterologous viral structural protein comprises a sequence of SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 52, or SEQ ID NO: 53; wherein T is a target binding domain and S1 is a stalk portion, wherein the target binding domain comprises an amino acid sequence of SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 50, or SEQ ID NO: 51; wherein the stalk portion S1 comprises a formula of L3-X1; wherein L3 is a flexible peptide linker having an amino acid sequence of SEQ ID NO: 55; and X1 is a polypeptide comprising a transmembrane domain having a formula ECD-TM-ICD, wherein ECD is an extracellular domain having an amino acid sequence
  • the heterologous viral structural protein comprises a sequence of SEQ ID NO: 22. In some embodiments, the heterologous viral structural protein comprises a sequence of SEQ ID NO: 23. In some embodiments, the heterologous viral structural protein comprises a sequence of SEQ ID NO: 24. In some embodiments, the heterologous viral structural protein comprises a sequence of SEQ ID NO: 25. In some embodiments, the heterologous viral structural protein comprises a sequence of SEQ ID NO: 52. In some embodiments, the heterologous viral structural protein comprises a sequence of SEQ ID NO: 53. In some embodiments, the target binding domain has an amino acid sequence of SEQ ID NO: 38. In some embodiments, the target binding domain has an amino acid sequence of SEQ ID NO: 39.
  • the target binding domain has an amino acid sequence of SEQ ID NO: 50. In some embodiments, the target binding domain has an amino acid sequence of SEQ ID NO: 51. In some embodiments, L3 has an amino acid sequence of SEQ ID NO: 55. In some embodiments, the ECD has an amino acid sequence of SEQ ID NO: 59. In some embodiments, the TM has an amino acid sequence of SEQ ID NO: 61. In some embodiments, the env incorporation motif has an amino acid sequence of SEQ ID NO: 63. In some embodiments, the env incorporation motif has an amino acid sequence of SEQ ID NO: 64. In some embodiments, the viral particle further comprises a nucleic acid molecule encoding a heterologous molecule of interest.
  • the heterologous molecule of interest is as provided for herein.
  • the heterologous molecule of interest is a CAR as provided for herein.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 99, at least 90% identity to SEQ ID NO: 99, at least 95% identity to SEQ ID NO: 99. at least 99% identity to SEQ ID NO: 99, or at least 100% identity to SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 105, at least 90% identity to SEQ ID NO: 105, at least 95% identity to SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 106, at least 90% identity to SEQ ID NO: 106, at least 95% identity to SEQ ID NO: 106. at least 99% identity to SEQ ID NO: 106, or at least 100% identity to SEQ ID NO: 106. In some embodiments, the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 107, at least 90% identity to SEQ ID NO: 107, at least 95% identity to SEQ ID NO: 107.
  • a viral particle comprising a heterologous viral structural protein and a targeting moiety, wherein the targeting moiety comprises a polypeptide having a formula of T-S1, wherein the heterologous viral structural protein comprises a sequence of SEQ ID NO: 23 or SEQ ID NO: 25; wherein T is a target binding domain and S1 is a stalk portion, wherein the target binding domain comprises an amino acid sequence of SEQ ID NO: 39; wherein the stalk portion S1 comprises a formula of L3-X1; wherein L3 is a flexible peptide linker having an amino acid sequence of SEQ ID NO: 55; and X1 is a polypeptide comprising a transmembrane domain having a formula ECD-TM- ICD, wherein ECD is an extracellular
  • the heterologous viral structural protein comprises a sequence of SEQ ID NO: 23. In some embodiments, the heterologous viral structural protein comprises a sequence of SEQ ID NO: 25. In some embodiments, the target binding domain has an amino acid sequence of SEQ ID NO: 39. In some embodiments, L3 has an amino acid sequence of SEQ ID NO: 55. In some embodiments, the ECD has an amino acid sequence of SEQ ID NO: 59. In some embodiments, the TM has an amino acid sequence of SEQ ID NO: 61. In some embodiments, the env incorporation motif has an amino acid sequence of SEQ ID NO: 63. In some embodiments, the env incorporation motif has an amino acid sequence of SEQ ID NO: 64.
  • the viral particle further comprises a nucleic acid molecule encoding a heterologous molecule of interest.
  • the heterologous molecule of interest is as provided for herein.
  • the heterologous molecule of interest is a CAR as provided for herein.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 99, at least 90% identity to SEQ ID NO: 99, at least 95% identity to SEQ ID NO: 99. at least 99% identity to SEQ ID NO: 99, or at least 100% identity to SEQ ID NO: 99.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 105, at least 90% identity to SEQ ID NO: 105, at least 95% identity to SEQ ID NO: 105. at least 99% identity to SEQ ID NO: 105, or at least 100% identity to SEQ ID NO: 105. In some embodiments, the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 106, at least 90% identity to SEQ ID NO: 106, at least 95% identity to SEQ ID NO: -192- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT 106. at least 99% identity to SEQ ID NO: 106, or at least 100% identity to SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 107, at least 90% identity to SEQ ID NO: 107, at least 95% identity to SEQ ID NO: 107. at least 99% identity to SEQ ID NO: 107, or at least 100% identity to SEQ ID NO: 107.
  • a viral particle comprising a heterologous viral structural protein and a targeting moiety, wherein the targeting moiety comprises a polypeptide having a formula of T-S1, wherein the heterologous viral structural protein comprises a sequence of SEQ ID NO: 52 or SEQ ID NO: 53; wherein T is a target binding domain and S 1 is a stalk portion, wherein the target binding domain comprises an amino acid sequence of SEQ ID NO: 39; wherein the stalk portion S1 comprises a formula of L3-X1; wherein L3 is a flexible peptide linker having an amino acid sequence of SEQ ID NO: 55; and X1 is a polypeptide comprising a transmembrane domain having a formula ECD-TM- ICD, wherein ECD is an extracellular domain having an amino acid sequence of SEQ ID NO: 59, or is a fragment thereof, or is absent; TM is a transmembrane domain having an amino acid sequence of SEQ ID NO: 61, or
  • the heterologous viral structural protein comprises a sequence of SEQ ID NO: 52. In some embodiments, the heterologous viral structural protein comprises a sequence of SEQ ID NO: 53. In some embodiments, the target binding domain has an amino acid sequence of SEQ ID NO: 39. In some embodiments, L3 has an amino acid sequence of SEQ ID NO: 55. In some embodiments, the ECD has an amino acid sequence of SEQ ID NO: 59. In some embodiments, the TM has an amino acid sequence of SEQ ID NO: 61. In some embodiments, the env incorporation motif has an amino acid sequence of SEQ ID NO: 63. In some embodiments, the env incorporation motif has an amino acid sequence of SEQ ID NO: 64.
  • the viral particle further comprises a nucleic acid molecule encoding a heterologous molecule of interest.
  • the heterologous molecule of interest is as provided for herein.
  • the heterologous molecule of interest is a CAR as provided for herein.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 99, at least 90% identity to SEQ ID NO: 99, at least 95% identity to SEQ ID NO: 99. at least 99% identity to SEQ ID NO: 99, or at least 100% identity to SEQ ID NO: 99.
  • the CAR -193- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 105, at least 90% identity to SEQ ID NO: 105, at least 95% identity to SEQ ID NO: 105. at least 99% identity to SEQ ID NO: 105, or at least 100% identity to SEQ ID NO: 105.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 106, at least 90% identity to SEQ ID NO: 106, at least 95% identity to SEQ ID NO: 106. at least 99% identity to SEQ ID NO: 106, or at least 100% identity to SEQ ID NO: 106.
  • the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 107, at least 90% identity to SEQ ID NO: 107, at least 95% identity to SEQ ID NO: 107. at least 99% identity to SEQ ID NO: 107, or at least 100% identity to SEQ ID NO: 107.
  • a pharmaceutical composition comprising the envelope pseudotyped viral particles or vectors as provided for herein, i.e. a particle that comprises a VSV-G mutant protein provided for herein.
  • methods of delivering a cargo of interest to a cell are provided.
  • the methods comprise contacting the cell with the pseudotyped viral- like particles or viral vectors as provided for herein, or a pharmaceutical composition comprising the same.
  • methods of delivering a cargo of interest to a cell in a subject are provided.
  • the methods comprise administering to the subject the pseudotyped viral-like particles or viral vectors as provided for herein, or a pharmaceutical composition comprising the same.
  • the cargo is a chimeric antigen receptor or as otherwise provided for herein.
  • methods for of delivering a chimeric antigen receptor to a T- cell in a subject are provided.
  • the methods comprising administering to the subject the pseudotyped viral-like particles or viral vectors as provided for herein, or a pharmaceutical composition comprising the same, wherein the pseudotyped viral-like particle or viral vector comprises a heterologous nucleic acid molecule encoding the chimeric antigen receptor.
  • nucleic acid molecules encoding a mutant VSV-G protein as provided for herein. Methods of making the viral like particles or vectors comprising a mutant VSV-G protein are also provided.
  • the methods comprise transfecting or transducing a packaging cell line with the nucleic acid molecules encoding a mutant VSV-G protein as provided for herein under conditions sufficient to produce the pseudotyped viral-like -194- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT particles or viral vectors.
  • the methods comprise transfecting or transducing a packaging cell line with the plurality of nucleic acid molecules provided for herein under conditions sufficient to produce the pseudotyped viral-like particles or viral vectors.
  • methods further comprise isolating the pseudotyped viral-like particle or viral vector.
  • the nucleic acid molecules also comprise a nucleic acid molecule encoding a targeting moiety and/or a cargo that is to be delivered by the viral vector that is produced.
  • Methods of Treating a Disease or Disorder Also provided for herein are methods of treating a disease or disorder in a s subject in need thereof.
  • the methods comprise administering to the subject the pseudotyped viral-like particles or viral vectors as provided for herein, or a pharmaceutical composition comprising the same, wherein the pseudotyped viral-like particle or viral vector comprises a heterologous nucleic acid molecule encoding the chimeric antigen receptor.
  • the disease or disorder is any disease or disorder wherein a chimeric antigen receptor as provided for herein would be useful for the treatment of said disease or disorder.
  • the disease or disorder is cancer (e.g. such as a T cell or B cell disorder or other types of cancer as described herein), an immune disorder, an auto-immune disorder, metabolic disorder, and the like.
  • the immune disorder is selected from multiple sclerosis (MS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), lupus nephritis (LN), warm autoimmune hemolytic anemia (WAHA), primary sclerosing cholangitis (PSC), or IgG4-related disease (IGG4-RD).
  • MS multiple sclerosis
  • SLE systemic lupus erythematosus
  • SSc systemic sclerosis
  • LN lupus nephritis
  • WAHA warm autoimmune hemolytic anemia
  • PSC primary sclerosing cholangitis
  • IgG4-RD IgG4-related disease
  • Immune disorders may also be selected from acute disseminated encephalomyelitis (ADEM), Evans’ syndrome (ES), focal segmental glomerulosclerosis (FSGS), Mixed connective tissue disease (MCTD), Mooren’s ulcer (MU), chronic inflammatory demyelinating polyneuropathy (CIDP), Membranous nephropathy (MN), or thyroid eye disease (TED).
  • the immune disorder is multiple sclerosis (MS).
  • the immune disorder is systemic lupus erythematosus (SLE).
  • the immune disorder is systemic sclerosis (SSc).
  • the immune disorder is lupus nephritis (LN).
  • the immune disorder is warm autoimmune hemolytic anemia (WAHA). In some embodiments, the immune disorder is primary sclerosing cholangitis (PSC). In some embodiments, the immune disorder is or IgG4-related disease (IGG4-RD). In some embodiments, the immune disorder is acute disseminated encephalomyelitis (ADEM). In some embodiments, the immune disorder is Evans’ syndrome (ES). In some embodiments, the -195- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT immune disorder is focal segmental glomerulosclerosis (FSGS). In some embodiments, the immune disorder is Mixed connective tissue disease (MCTD). In some embodiments, the immune disorder is Mooren’s ulcer (MU).
  • WAHA warm autoimmune hemolytic anemia
  • PSC primary sclerosing cholangitis
  • IgG4-RD IgG4-related disease
  • the immune disorder is acute disseminated encephalomyelitis (ADEM).
  • the immune disorder is chronic inflammatory demyelinating polyneuropathy (CIDP).
  • the immune disorder is Membranous nephropathy (MN).
  • the immune disorder is thyroid eye disease (TED).
  • the viral particles provided herein may be used to target CD7 positive T-cells and deliver a chimeric antigen receptor targeting CD19 (CD19 CAR) such as those provided for herein.
  • CD19 CAR chimeric antigen receptor targeting CD19
  • the CD19 CAR cells then deplete the CD19 positive B-cell population, which results in treatment of immune/autoimmune diseases and disorders, as provided for herein.
  • methods of treating cancer in a subject are also provided for herein.
  • the methods comprise administering to the subject the pseudotyped viral-like particles or viral vectors as provided for herein, or a pharmaceutical composition comprising the same, wherein the pseudotyped viral-like particle or viral vector comprises a heterologous nucleic acid molecule encoding the chimeric antigen receptor.
  • the methods comprise administering to the subject immune cells that have been transduced by the pseudotyped viral-like particle or viral vectors as provided for herein.
  • the immune cells are first isolated from the subject prior to transduction by the pseudotyped viral-like particle or viral vectors as provided for herein. Also provided herein are methods of treating a disease in a subject in need thereof.
  • the methods provided include, but are not limited to, methods of treating a disease in a subject in need thereof, comprising administering to the subject the viral particle(s) provided herein to treat the disease.
  • the disease is a cancer.
  • the compositions provided for herein can be used in methods for the treatment of any condition related to a cancer, such as a cell-mediated immune response against a tumor cell(s), where it is desirable to treat or alleviate the disease.
  • the types of cancers to be treated include, but are not limited to, carcinoma, blastoma, sarcoma, certain leukemia or lymphoid malignancies, benign and malignant tumors, malignancies e.g., sarcomas, carcinomas, and melanomas.
  • Other exemplary cancers include, but are not limited to, breast cancer, prostate cancer, ovarian cancer, cervical cancer, skin cancer, pancreatic cancer, colorectal cancer, renal cancer, liver cancer, brain cancer, lymphoma, leukemia, lung cancer, thyroid cancer, and the like.
  • the cancers may be -196- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT non-solid tumors (such as hematological tumors) or solid tumors.
  • the cancer is a hematological tumor.
  • the cancer is a carcinoma.
  • the cancer is a sarcoma.
  • the cancer is a leukemia.
  • the cancer is lymphoma.
  • the cancer is a solid tumor.
  • Solid tumors are abnormal masses of tissue that usually do not contain cysts or liquid areas. Solid tumors can be benign or malignant.
  • solid tumors are named for the type of cells that form them (such as sarcomas, carcinomas, and lymphomas).
  • solid tumors such as sarcomas and carcinomas, include fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteosarcoma, synovioma, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, lymphoid malignancy, pancreatic cancer, breast cancer, lung cancers, ovarian cancer, prostate cancer, hepatocellular carcinoma, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, medullary thyroid carcinoma, papillary thyroid carcinoma, pheochromocytomas sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, he
  • Carcinomas that can be amenable to therapy by the methods disclosed herein include, but are not limited to, esophageal carcinoma, hepatocellular carcinoma, basal cell carcinoma (a form of skin cancer), squamous cell carcinoma (various tissues), bladder carcinoma, including transitional cell carcinoma (a malignant neoplasm of the bladder), bronchogenic carcinoma, colon carcinoma, colorectal carcinoma, gastric carcinoma, lung carcinoma, including small cell carcinoma and non-small cell carcinoma of the lung, adrenocortical carcinoma, thyroid carcinoma, pancreatic carcinoma, breast carcinoma, ovarian carcinoma, prostate carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinoma, cystadenocarcinoma, medullary carcinoma, renal cell carcinoma, ductal carcinoma in situ or bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilm's tumor, cervical carcinoma, uterine carcinoma, -197-
  • compositions provided herein can be used in methods to treat a myeloma, or a condition related to myeloma.
  • myeloma or conditions related thereto include, without limitation, light chain myeloma, non-secretory myeloma, monoclonal gamopathy of undertermined significance (MGUS), plasmacytoma (e.g., solitary, multiple solitary, extramedullary plasmacytoma), amyloidosis, and multiple myeloma.
  • methods of treating multiple myeloma are provided.
  • the multiple myeloma is refractory myeloma.
  • the multiple myeloma is relapsed myeloma.
  • the in vivo modified immune cells produced using the compositions provided herein are used to treat a melanoma, or a condition related to melanoma.
  • melanoma or conditions related thereto include, without limitation, superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma, acral lentiginous melanoma, amelanotic melanoma, or melanoma of the skin (e.g., cutaneous, eye, vulva, vagina, rectum melanoma).
  • the melanoma is cutaneous melanoma In some embodiments, the melanoma is refractory melanoma. In some embodiments, the melanoma is relapsed melanoma. In some embodiments, the compositions provided herein are used to treat a sarcoma, or a condition related to sarcoma.
  • sarcoma or conditions related thereto include, without limitation, angiosarcoma, chondrosarcoma, chordoma, endotheliosarcoma, Ewing’s sarcoma, fibrosarcoma, gastrointestinal stromal tumor, leiomyosarcoma, liposarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, mesothelioma, malignant peripheral nerve sheath tumor, myxosarcoma, osteogenic sarcoma, osteosarcoma, pleomorphic sarcoma, rhabdomyosarcoma, synovioma, synovial sarcoma, and other soft tissue sarcomas.
  • the sarcoma is synovial sarcoma.
  • the sarcoma is liposarcoma such as myxoid/round cell liposarcoma, differentiated/dedifferentiated liposarcoma, or pleomorphic liposarcoma.
  • the sarcoma is myxoid/round cell liposarcoma.
  • the sarcoma is refractory sarcoma.
  • the sarcoma is relapsed sarcoma.
  • the subject has been treated with a therapeutic agent targeting the disease or condition, e.g. the tumor, prior to administration of the composition.
  • the subject is refractory or non-responsive to the other therapeutic agent.
  • the subject has persistent or relapsed disease, e.g., following treatment with -198- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT another therapeutic intervention, including chemotherapy, radiation, and/or hematopoietic stem cell transplantation (HSCT), e.g., allogenic HSCT.
  • HSCT hematopoietic stem cell transplantation
  • the administration effectively treats the subject despite the subject having become resistant to another therapy.
  • the subject is responsive to the other therapeutic agent, and treatment with the therapeutic agent reduces disease burden.
  • the subject is initially responsive to the therapeutic agent, but exhibits a relapse of the disease or condition over time.
  • the subject has not relapsed.
  • the subject is determined to be at risk for relapse, such as at a high risk of relapse, and thus the composition is administered prophylactically, e.g., to reduce the likelihood of or prevent relapse.
  • the subject has not received prior treatment with another therapeutic agent.
  • the administration of the compositions may be carried out in any convenient manner known to those of skill in the art.
  • the compositions may be administered to a subject by aerosol inhalation, injection, ingestion, transfusion, implantation or transplantation.
  • compositions described herein may be administered to a patient transarterially, subcutaneously, intradermally, intratumorally, intranodally, intramedullary, intramuscularly, by intravenous (i.v.) injection, intraperitoneally, intranasally, intracranially, or intraosseously.
  • the compositions is injected directly into a site of a local disease site in the subject, a lymph node, an organ, a tumor, and the like.
  • the appropriate dosage may depend on the type of disease to be treated, the severity and course of the disease, whether the composition is administered for preventive or therapeutic purposes, previous therapy, the subject's clinical history and response to the treatment, and the discretion of the attending physician.
  • composition is, in some embodiments, suitably administered to the subject at one time or over a series of treatments.
  • the composition is administered as part of a combination treatment, such as simultaneously with or sequentially with, in any order, another therapeutic intervention, such as an antibody or produced cell or receptor or agent, such as a cytotoxic or therapeutic agent.
  • another therapeutic intervention such as an antibody or produced cell or receptor or agent, such as a cytotoxic or therapeutic agent.
  • the composition(s) in some embodiments, is co-administered with one or more additional therapeutic agents or in connection with another therapeutic intervention, either simultaneously or sequentially in any order.
  • the composition is co- administered with another therapy sufficiently close in time such that the composition enhances the effect of one or more additional therapeutic agents, or vice versa.
  • the composition is administered prior to the one or more additional therapeutic agents. In some embodiments, the composition is administered after the one or more additional therapeutic agents. In some embodiments, the one or more additional agents includes a cytokine, such as IL-2, for example, to enhance persistence. In some embodiments, the methods comprise administration of a chemotherapeutic agent. In some embodiments, the methods do not comprise the administration of a chemotherapeutic agent. In certain embodiments, the compositions may be administered to a subject in combination with an immune checkpoint antibody (e.g., an anti-PD1, anti-CTLA-4, or anti- PDL1 antibody).
  • an immune checkpoint antibody e.g., an anti-PD1, anti-CTLA-4, or anti- PDL1 antibody.
  • viral vectors may be administered in combination with an antibody or antibody fragment targeting, for example, PD-1 (programmed death 1 protein).
  • PD-1 programmed death 1 protein
  • anti-PD-1 antibodies include, but are not limited to, pembrolizumab (KEYTRUDA®, formerly lambrolizumab, also known as MK-3475), and nivolumab (BMS- 936558, MDX-1106, ONO-4538, OPDIVO®) or an antigen-binding fragment thereof.
  • the compositions may be administered in combination with an anti-PD- L1 antibody or antigen-binding fragment thereof.
  • anti-PD-L1 antibodies examples include, but are not limited to, BMS-936559, MPDL3280A (TECENTRIQ®, Atezolizumab), and MEDI4736 (Durvalumab, Imfinzi).
  • the composition may be administered in combination with an anti-CTLA-4 antibody or antigen-binding fragment thereof.
  • An example of an anti- CTLA-4 antibody includes, but is not limited to, Ipilimumab (trade name Yervoy).
  • Other types of immune checkpoint modulators may also be used including, but not limited to, small molecules, siRNA, miRNA, and CRISPR systems. Immune checkpoint modulators may be administered before, after, or concurrently with the viral vector.
  • combination treatment comprising an immune checkpoint modulator may increase the therapeutic efficacy of a therapy comprising a composition as provided herein.
  • the other therapeutic can be administered simultaneously, before, or after the compositions provided herein are administered to the subject.
  • the subject is provided a secondary treatment. Secondary treatments include but are not limited to chemotherapy, radiation, surgery, and medications.
  • the subject is not provided a secondary treatment.
  • the methods are performed without a lymphodepletion step, such as the administration of cyclophosphamide and/or fludarabine.
  • the subject can be administered a conditioning therapy after the administration of the compositions to kill certain immune cells that are not transduced with the CAR encoded by the compositions.
  • the conditioning therapy comprises administering an effective amount of cyclophosphamide to the subject. In some embodiments, the conditioning therapy comprises administering an effective amount of fludarabine to the subject. In some embodiments, the conditioning therapy comprises administering an effective amount of a combination of cyclophosphamide and fludarabine to the subject. In some embodiments, a specific dosage regimen of the present disclosure includes a lymphodepletion step after the administration of the composition.
  • the lymphodepletion step includes administration of cyclophosphamide and/or fludarabine. In some embodiments, the lymphodepletion step includes administration of cyclophosphamide at a dose of between about 200 mg/m 2 /day and about 2000 mg/m 2 /day (e.g., 200 mg/m 2 /day, 300 mg/m 2 /day, or 500 mg/m 2 /day). In an exemplary embodiment, the dose of cyclophosphamide is about 300 mg/m 2 /day.
  • the lymphodepletion step includes administration of fludarabine at a dose of between about 20 mg/m 2 /day and about 900 mg/m 2 /day (e.g., 20 mg/m 2 /day, 25 mg/m 2 /day, 30 mg/m 2 /day, or 60 mg/m 2 /day).
  • the dose of fludarabine is about 30 mg/m 2 /day.
  • the lymphodepletion step includes administration of cyclophosphamide at a dose of between about 200 mg/m 2 /day and about 2000 mg/m 2 /day (e.g., 200 mg/m 2 /day, 300 mg/m 2 /day, or 500 mg/m 2 /day), and fludarabine at a dose of between about 20 mg/m 2 /day and about 900 mg/m 2 /day (e.g., 20 mg/m 2 /day, 25 mg/m 2 /day, 30 mg/m 2 /day, or 60 mg/m 2 /day).
  • cyclophosphamide at a dose of between about 200 mg/m 2 /day and about 2000 mg/m 2 /day (e.g., 200 mg/m 2 /day, 300 mg/m 2 /day, or 500 mg/m 2 /day)
  • fludarabine at a dose of between about 20 mg/m 2 /day and about 900 mg/m 2 /day (e
  • the lymphodepletion step includes administration of cyclophosphamide at a dose of about 300 mg/m 2 /day, and fludarabine at a dose of about 30 mg/m 2 /day.
  • the dosing of cyclophosphamide is 300 mg/m 2 /day over three days
  • the dosing of fludarabine is 30 mg/m 2 /day over three days.
  • CRS cytokine release syndrome
  • CRS CRS is a known on-target toxicity, development of which likely correlates with efficacy.
  • Clinical and laboratory measures range from mild CRS (constitutional symptoms and/or grade-2 organ toxicity) to severe CRS (sCRS; grade ⁇ 3 organ toxicity, aggressive clinical intervention, and/or potentially life threatening).
  • Clinical features include: high fever, malaise, fatigue, myalgia, nausea, anorexia, tachycardia/hypotension, capillary leak, cardiac dysfunction, renal impairment, hepatic failure, -201- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT and disseminated intravascular coagulation.
  • CRS C-reactive protein
  • the methods comprise, following the diagnosis of CRS, appropriate CRS management strategies to mitigate the physiological symptoms of uncontrolled inflammation without dampening the antitumor efficacy of the in vivo generated cells (e.g., CAR T cells).
  • CRS management strategies are known in the art.
  • systemic corticosteroids may be administered to rapidly reverse symptoms of sCRS (e.g., grade 3 CRS) without compromising initial antitumor response.
  • an anti-IL-6R antibody may be administered.
  • an anti-IL-6R antibody is the Food and Drug Administration-approved monoclonal antibody tocilizumab, also known as atlizumab (marketed as Actemra, or RoActemra).
  • Tocilizumab is a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R).
  • IL-6R interleukin-6 receptor
  • Administration of tocilizumab has demonstrated near-immediate reversal of CRS.
  • CRS is generally managed based on the severity of the observed syndrome and interventions are tailored as such. CRS management decisions may be based upon clinical signs and symptoms and response to interventions, not solely on laboratory values alone.
  • the first-line management of CRS may be tocilizumab, in some embodiments, at the labeled dose of 8 mg/kg IV over 60 minutes (not to exceed 800 mg/dose); tocilizumab can be repeated Q8 hours. If suboptimal response to the first dose of tocilizumab, additional doses of tocilizumab may be considered.
  • Tocilizumab can be administered alone or in combination with corticosteroid therapy.
  • INH-029WO PATENT may be treated with high-dose corticosteroid therapy, generally hydrocortisone 100 mg IV or methylprednisolone 1-2 mg/kg.
  • corticosteroid therapy generally hydrocortisone 100 mg IV or methylprednisolone 1-2 mg/kg.
  • patients may be administered high-dose corticosteroid therapy early in the course of the CRS.
  • CRS management guidance may be based on published standards (Lee et al. (2019) Biol Blood Marrow Transplant, doi.org/10.1016/j.bbmt.2018.12.758; Neelapu et al.
  • MAS Macrophage Activation Syndrome
  • HHLH Hemophagocytic lymphohistiocytosis
  • MAS appears to be a reaction to immune activation that occurs from the CRS, and should therefore be considered a manifestation of CRS.
  • MAS is similar to HLH (also a reaction to immune stimulation).
  • the clinical syndrome of MAS is characterized by high grade non-remitting fever, cytopenias affecting at least two of three lineages, and hepatosplenomegaly.
  • compositions disclosed herein can comprise a pharmaceutical composition, and for example include a pharmaceutically acceptable carrier, and/or a pharmaceutical formulation.
  • pharmaceutical formulation refers to a preparation which is in such form as to permit the biological activity of an active ingredient contained therein to be effective, and which contains no additional components which are unacceptably toxic to a subject to which the formulation would be administered.
  • a “pharmaceutically acceptable carrier” refers to an ingredient in a pharmaceutical formulation, other than an active ingredient, which is nontoxic to a subject.
  • a pharmaceutically acceptable carrier includes, but is not limited to, a buffer, excipient, stabilizer, or preservative.
  • the choice of carrier is determined in part by the particular cell and/or by the method of administration. Accordingly, there are a variety of suitable formulations.
  • the pharmaceutical composition can contain preservatives. Suitable preservatives may include, for example, methylparaben, propylparaben, sodium benzoate, and benzalkonium chloride. In some aspects, a mixture of two or more preservatives is used.
  • the preservative or mixtures thereof are typically present in an amount -203- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT of about 0.0001% to about 2% by weight of the total composition.
  • Carriers are described, e.g., by Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980).
  • Pharmaceutically acceptable carriers are generally nontoxic to recipients at the dosages and concentrations employed, and include, but are not limited to: buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride; benzethonium chloride; phenol, butyl or benzyl alcohol; alkyl parabens such as methyl or propyl paraben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arg
  • Buffering agents in some aspects are included in the compositions. Suitable buffering agents include, for example, citric acid, sodium citrate, phosphoric acid, potassium phosphate, and various other acids and salts. In some aspects, a mixture of two or more buffering agents is used. The buffering agent or mixtures thereof are typically present in an amount of about 0.001% to about 4% by weight of the total composition. Methods for preparing administrable pharmaceutical compositions are known. Exemplary methods are described in more detail in, for example, Remington: The Science and Practice of Pharmacy, Lippincott Williams & Wilkins; 21st ed. (May 1, 2005).
  • the formulations can include aqueous solutions.
  • the formulation or composition may also contain more than one active ingredient useful for the particular indication, disease, or condition being treated with the composition, preferably those with activities complementary to the composition, where the respective activities do not adversely affect one another.
  • active ingredients are suitably present in combination in amounts that are effective for the purpose intended.
  • the pharmaceutical composition further includes other pharmaceutically active agents or drugs, such as chemotherapeutic agents, e.g., asparaginase, busulfan, carboplatin, cisplatin, daunorubicin, doxorubicin, fluorouracil, gemcitabine, hydroxyurea, methotrexate, paclitaxel, rituximab, vinblastine, and/or vincristine.
  • chemotherapeutic agents e.g., asparaginase, busulfan, carboplatin, cisplatin, daunorubicin, doxorubicin, fluorouracil, gemcitabine, hydroxyurea, methotrexate, paclitaxel, rituximab, vinblastine, and/or vincristine.
  • the pharmaceutical composition in some embodiments contains the composition in amounts effective to treat or prevent the disease or condition, such as a therapeutically effective or -204- IPTS/128579164.3 DOCKET NO:
  • Therapeutic or prophylactic efficacy in some embodiments is monitored by periodic assessment of treated subjects.
  • the desired dosage can be delivered by a single bolus administration of the composition, by multiple bolus administrations of the composition, or by continuous infusion administration of the composition.
  • the pharmaceutical composition does not include a chemotherapeutic.
  • Formulations include those for oral, intravenous, intraperitoneal, subcutaneous, pulmonary, transdermal, intramuscular, intranasal, buccal, sublingual, or suppository administration.
  • the composition is administered parenterally.
  • parenteral includes intravenous, intramuscular, subcutaneous, rectal, vaginal, and intraperitoneal administration.
  • compositions in some embodiments are provided as sterile liquid preparations, e.g., isotonic aqueous solutions, suspensions, emulsions, dispersions, or viscous compositions, which may in some aspects be buffered to a selected pH.
  • sterile liquid preparations e.g., isotonic aqueous solutions, suspensions, emulsions, dispersions, or viscous compositions, which may in some aspects be buffered to a selected pH.
  • Liquid preparations are normally easier to prepare than gels, other viscous compositions, and solid compositions. Additionally, liquid compositions are somewhat more convenient to administer, especially by injection. Viscous compositions, on the other hand, can be formulated within the appropriate viscosity range to provide longer contact periods with specific tissues.
  • Liquid or viscous compositions can comprise carriers, which can be a solvent or dispersing medium containing, for example, water, saline, phosphate buffered saline, polyol (for example, glycerol, propylene glycol, liquid polyethylene glycol) and suitable mixtures thereof.
  • Sterile injectable solutions can be prepared by incorporating the composition in a solvent, such as in admixture with a suitable carrier, diluent, or excipient such as sterile water, physiological saline, glucose, dextrose, or the like.
  • compositions can contain auxiliary substances such as wetting, dispersing, or emulsifying agents (e.g., methylcellulose), pH buffering agents, gelling or viscosity enhancing additives, preservatives, flavoring agents, and/or colors, depending upon the route of administration and the preparation desired. Standard texts may in some aspects be consulted to prepare suitable preparations.
  • auxiliary substances such as wetting, dispersing, or emulsifying agents (e.g., methylcellulose), pH buffering agents, gelling or viscosity enhancing additives, preservatives, flavoring agents, and/or colors, depending upon the route of administration and the preparation desired. Standard texts may in some aspects be consulted to prepare suitable preparations.
  • Various additives which enhance the stability and sterility of the compositions including antimicrobial preservatives, antioxidants, chelating agents, and buffers, can be added. Prevention of the action of microorganisms can be ensured by various antibacterial and antifungal agents, for example, parabens, chlor
  • Prolonged absorption of the injectable pharmaceutical form can be brought about by the use of agents delaying absorption, for example, aluminum monostearate and gelatin.
  • agents delaying absorption for example, aluminum monostearate and gelatin.
  • the formulations to be used for in vivo administration are generally sterile. Sterility may be readily accomplished, e.g., by filtration through sterile filtration membranes.
  • the embodiments provided for herein can be used for many purposes, since the a pseudotyped virus capable of fusing with a target cell can be used to deliver a gene or other heterologous sequence of interest. Enumerated Embodiments In some embodiments, the following embodiments are provided: 1.
  • a viral particle comprising a heterologous viral glycoprotein and a targeting moiety, wherein the targeting moiety comprises a polypeptide having the formula T-S1, wherein T is a target binding domain and S1 is a stalk portion.
  • the stalk portion S1 comprises a variant Fc protein, wherein the variant Fc protein comprises a transmembrane domain and an effector mutation, wherein the effector mutation inhibits the interaction between the Fc protein and a Fc interacting protein, such as Fc ⁇ R, C1q, FcR ⁇ , or FcRn.
  • the viral particle of embodiment 2, wherein the S1 stalk portion is attached to the surface of the viral particle through the transmembrane domain. 4.
  • the viral particle of embodiment 18, wherein the variant IgG2 Fc protein comprises one or more mutations selected from the group consisting of: N297A, P329G, I253A, H310A, and H435A. 20.
  • L1 and L2 are each, independently, a polypeptide linker.
  • the polypeptide linker comprises (GGGGA)n (SEQ ID NO: 54), (GGGGS)n (SEQ ID NO: 55), (EAAAK)n (SEQ ID NO: 73), A(EAAAK)nA (SEQ ID NO: 74), (XP)n (SEQ ID NO: 75), wherein X is Ala, Lys, or Glu, GSAGSAAGSGEF (SEQ ID NO: 56), KESGSVSSEQLAQFRSLD (SEQ ID NO: 57), EGKSSGSGSESKST (SEQ ID NO: 58), AEAAAKEAAAKA (SEQ ID NO: 76), or a combination thereof, wherein each n is, independently, 1-5. 41.
  • X1 comprises a polypeptide having a formula of ECD-TM-ICD, wherein: ECD is an extracellular domain, or a fragment thereof, of a cell surface protein, or absent; TM is a transmembrane domain of a transmembrane protein; and ICD is an intracellular domain or a protein that facilitates incorporation of the targeting moiety into the envelope of the viral particle, or absent, wherein the targeting moiety having the formula of T-L1-Fc-L2-X1 has a formula of T-L1-Fc- L2-ECD-TM-ICD. 46.
  • the viral particle of embodiment 45, wherein the ECD is an extracellular domain, or fragment thereof, of CD8 or CD28. 48.
  • the viral particle of embodiment 47, wherein the ECD comprises an amino acid sequence of SEQ ID NO: 59 or SEQ ID NO: 60.
  • the viral particle of embodiment 47, wherein the ECD comprises an amino acid sequence of SEQ ID NO: 60. 50.
  • the viral particle of embodiment 50, wherein the TM comprises an amino acid sequence of SEQ ID NO: 61 or SEQ ID NO: 62. 52.
  • the viral particle of embodiment 50, wherein the TM comprises an amino acid sequence of SEQ ID NO: 62. 53.
  • the viral particle of any one of embodiments 45-52, wherein the ICD is absent.
  • the viral particle of any one of embodiments 45-52, wherein the ICD comprises an Env incorporation motif.
  • the viral particle of embodiment 54, wherein the Env incorporation motif comprises an amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64. 56.
  • L3 comprises a polypeptide having a sequence of (GGGGA)n (SEQ ID NO: 54), (GGGGS)n (SEQ ID NO: 55), GSAGSAAGSGEF (SEQ ID NO: 56), KESGSVSSEQLAQFRSLD (SEQ ID NO: 57), EGKSSGSGSESKST (SEQ ID NO: 58), or any combination thereof, wherein each n is, independently, 1-4. 58.
  • X1 comprises a polypeptide having a formula of ECD-TM-ICD, wherein: ECD is an extracellular domain, or a fragment thereof, of a cell surface protein, or absent; TM is a transmembrane domain of a transmembrane protein; and ICD is an intracellular domain or a protein that facilitates the incorporation of the targeting moiety into the envelope of the viral particle, or absent, -210- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT wherein the targeting moiety having the formula of T-L3-X1 has a formula of T-L3- ECD-TM-ICD. 60.
  • the viral particle of embodiment 59, wherein the ECD is absent. 61.
  • the viral particle of embodiment 59, wherein the ECD is an extracellular domain, or fragment thereof, or CD8 or CD28.
  • the viral particle of embodiment 61, wherein the ECD comprises an amino acid sequence of SEQ ID NO: 59 or SEQ ID NO: 60.
  • the viral particle of embodiment 61, wherein the ECD comprises an amino acid sequence of SEQ ID NO: 59. 64.
  • the viral particle of embodiment 64, wherein the TM comprises an amino acid sequence of SEQ ID NO: 61 or SEQ ID NO: 62. 66.
  • the viral particle of embodiment 64, wherein the TM comprises an amino acid sequence of SEQ ID NO: 61. 67.
  • the viral particle of any one of embodiments 59-66, wherein the ICD is absent.
  • the viral particle of any one of embodiments 59-66, wherein the ICD comprises an Env incorporation motif. 69.
  • the viral particle of embodiment 68, wherein the Env incorporation motif comprises an amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64. 70.
  • the target binding domain (T) binds to an immune cell
  • the immune cell is any of a T cell, B cell; NK cell, dendritic cell, neutrophils, macrophages, a cancer cell; or, for example, CD3+ T cell; CD4+ T cell; CD7+ T cell, CD8+ T cell; CD19+ B cell; CD19+ cancer cell; CD20+ B cell; CD20+ cancer cell, CD30+ lung epithelial cell; CD34+ haematopoietic stem cell; CD105+ endothelial cell; CD105+ haematopoietic stem cell; CD117+ haematopoietic stem cell; CD133+ cancer cell; EpCAM+ cancer cell; GluA2+ neuron; GluA4+ neuron; Haematopoietic stem cell; Hepatocyte; Her2/Neu+ cancer cell; NKG2D+ natural killer cell; SLC1A3+ astrocyte; SLC
  • the target binding domain (T) binds to CD7.
  • the target binding domain (T) comprises a polypeptide comprising: (i) a heavy chain variable region comprising heavy chain CDRl, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 30; the heavy chain CDR2 has the amino acid sequence of SEQ ID NO: 31; and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 32, or variants of any of the foregoing; and (ii) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 33; the light chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 34; and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 35; or variants of any of the foregoing
  • the viral particle of embodiment 73, wherein the heavy chain variable region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 36, wherein the polypeptide comprises the sequences of HCDR1 as set forth in SEQ ID NO: 30; HCDR2 as set forth in SEQ ID NO: 31; and HCDR3 as set forth in SEQ ID NO: 32.
  • the viral particle of embodiments 73 or 74, wherein the light chain variable region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 37, wherein the polypeptide comprises the sequences of LCDR1 as set forth in SEQ ID NO: 33; LCDR2 as set forth in SEQ ID NO: 34; and LCDR3 as set forth in SEQ ID NO: 35.
  • polypeptide comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 36, and the light chain variable region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 37, wherein polypeptide comprises the sequences of HCDR1 as set forth in SEQ ID NO: 30; HCDR2 as set forth in SEQ ID NO: 31; -214- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT HCDR3 as set forth in SEQ ID NO: 32; LCDR1 as set forth in SEQ ID NO: 33; LCDR2 as set forth in SEQ ID NO: 34; and LCDR3 as set forth in SEQ ID NO: 35.
  • the viral particle of any one of embodiments 72-82, wherein the target binding domain (T) that binds to CD7 comprises a polypeptide comprising a sequence having at least 90% sequence identity to SEQ ID NO: 38, at least 95% sequence identity to SEQ ID NO: 38, at least 99% sequence identity to SEQ ID NO: 38, or a sequence as set forth in SEQ ID NO: 38. 85.
  • the viral particle of any one of embodiments 72-82, wherein the target binding domain (T) that binds to CD7 comprises a polypeptide comprising a sequence having at least 90% sequence identity to SEQ ID NO: 39, having at least 95% sequence identity to SEQ ID NO: 39, having at least 99% sequence identity to SEQ ID NO: 39, or a sequence as set forth in SEQ ID NO: 39. -215- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT 86.
  • the viral particle of embodiment 71, wherein the target binding domain (T) binds to CD8. 87.
  • the target binding domain (T) comprises a polypeptide that comprises: a heavy chain variable region comprising heavy chain CDRl, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 42; the heavy chain CDR2 has the amino acid sequence of SEQ ID NO: 43; and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 44, or variants of any of the foregoing; and (ii) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 45; the light chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 46; and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 47; or variants of any of the foregoing.
  • the viral particle of embodiment 87, wherein the target binding domain (T) comprises a heavy chain variable region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 48, wherein the polypeptide comprises the sequences of HCDR1 as set forth in SEQ ID NO: 42; HCDR2 as set forth in SEQ ID NO: 43; and HCDR3 as set forth in SEQ ID NO: 44. 89.
  • the viral particle of embodiment 87 or 88, wherein the target binding domain (T) comprises a light chain variable region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 49, wherein the polypeptide comprises the sequences of LCDR1 as set forth in SEQ ID NO: 45; LCDR2 as set forth in SEQ ID NO: 46; and LCDR3 as set forth in SEQ ID NO: 47. 90.
  • the target binding domain (T) comprises a polypeptide comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 48, and the light chain variable region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 49, wherein polypeptide comprises the sequences of HCDR1 as set forth in SEQ ID NO: 42; HCDR2 as set forth in SEQ ID NO: 43; HCDR3 as set forth in SEQ ID NO: 44; LCDR1 as set forth in SEQ ID NO: 45; LCDR2 as set forth in SEQ ID NO: 46; and LCDR3 as set forth in SEQ ID NO: 47.
  • the target binding domain (T) comprises a polypeptide comprising a heavy chain variable region and a light chain variable region, where the heavy chain variable region comprises an amino acid sequence having at -216- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT least 90% sequence identity to SEQ ID NO: 48; and the light chain variable region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 49. 92.
  • the target binding domain (T) comprises a polypeptide comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 48; and the light chain variable region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 49. 93.
  • a linker such as a peptide linker.
  • the peptide linker comprises a sequence of (GGGGS)n (SEQ ID NO: 55), wherein each n is independently 1-5.
  • 98. The viral particle of any one of embodiments 87-94, wherein the heavy chain variable region and the light chain variable region are directly linked to one another and are not linked by a linker. 99.
  • the viral particle of any one of embodiments 86-97, wherein the target binding domain (T) that binds to CD8 comprises a polypeptide comprising a sequence having at least 90% sequence identity to SEQ ID NO: 50, at least 95% sequence identity to SEQ ID NO: 50, at least 99% sequence identity to SEQ ID NO: 50, or a sequence as set forth in SEQ ID NO: 50. 100.
  • the viral particle of any one of embodiments 86-97, wherein the target binding domain (T) that binds to CD8 comprises a polypeptide comprising a sequence having at least 90% sequence identity to SEQ ID NO: 51, having at least 95% sequence identity to SEQ ID NO: 51, having at least 99% sequence identity to SEQ ID NO: 51, or a sequence as set forth in SEQ ID NO: 51. -217- IPTS/128579164.3 DOCKET NO: INH-029WO PATENT 101.
  • the SVCV-G polypeptide comprises a polypeptide having at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 52 or SEQ ID NO: 53. 104.
  • the viral particle of embodiment 102 or 103, wherein the SVCV-G polypeptide comprises a polypeptide having at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 53.
  • the viral particle of embodiment 102 or 103, wherein the SVCV-G polypeptide comprises SEQ ID NO: 52 or SEQ ID NO: 53. 107.
  • the viral particle 109 wherein the VSV-G polypeptide comprises an amino acid sequence having at least 70% identity to SEQ ID NO: 2 and comprising a mutation at position 182 as compared to SEQ ID NO: 2. 112.
  • 117. The viral particle of any one of embodiments 109-114, wherein the VSV-G polypeptide comprises a sequence at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% to a sequence of SEQ ID NO: 5.

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Abstract

L'invention propose des particules virales comprenant une glycoprotéine virale hétérologue et une fraction de ciblage, la fraction de ciblage comprenant un polypeptide comprenant une formule de T-S1, T étant un domaine de liaison cible et S1 <sp /> étant une partie de tige. Comme proposé ici, les particules virales comprennent en outre une molécule d'acide nucléique codant pour une molécule hétérologue d'intérêt. Selon la présente invention, la molécule hétérologue d'intérêt peut être une CAR CD19. L'invention propose également des compositions les comprenant, ainsi que des méthodes d'utilisation de celles-ci.
PCT/US2024/033431 2023-06-12 2024-06-11 Compositions et procédés pour le traitement de troubles immunologiques Ceased WO2024258866A1 (fr)

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AU2024303971A AU2024303971A1 (en) 2023-06-12 2024-06-11 Compositions and methods for the treatment of immunological disorders
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IL325221A IL325221A (en) 2023-06-12 2024-06-11 Compositions and methods for treating immunological disorders
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