EP0650367A1 - Verhinderung interzellulärer wechselwirkungen mit chimären cd43-molekülen - Google Patents

Verhinderung interzellulärer wechselwirkungen mit chimären cd43-molekülen

Info

Publication number
EP0650367A1
EP0650367A1 EP93913851A EP93913851A EP0650367A1 EP 0650367 A1 EP0650367 A1 EP 0650367A1 EP 93913851 A EP93913851 A EP 93913851A EP 93913851 A EP93913851 A EP 93913851A EP 0650367 A1 EP0650367 A1 EP 0650367A1
Authority
EP
European Patent Office
Prior art keywords
cell
molecule
cell targeting
targeting molecule
binding portion
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP93913851A
Other languages
English (en)
French (fr)
Other versions
EP0650367A4 (de
Inventor
Blair Ardman
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Tufts Medical Center Inc
Original Assignee
New England Medical Center Hospitals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by New England Medical Center Hospitals Inc filed Critical New England Medical Center Hospitals Inc
Publication of EP0650367A1 publication Critical patent/EP0650367A1/de
Publication of EP0650367A4 publication Critical patent/EP0650367A4/de
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/7056—Lectin superfamily, e.g. CD23, CD72
    • C07K14/70564—Selectins, e.g. CD62
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70514—CD4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70525—ICAM molecules, e.g. CD50, CD54, CD102
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70542—CD106
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70546—Integrin superfamily
    • C07K14/70553—Integrin beta2-subunit-containing molecules, e.g. CD11, CD18
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70596—Molecules with a "CD"-designation not provided for elsewhere
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • 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
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • a negatively charged CD43 extracellular domain may be fused to the receptors VCAM-1 and ICAM-l to produce chimeric proteins CD43:VCAM-1 and CD43:ICAM-l; such proteins bind and coat the surface of certain types of leukocytes, blocking interaction with their endothelial counterreceptors and therefore the intracellular interaction between the immune cells and the endothelium which leads to inflammation.
  • the cotransfected cells were screened by immunofluorescence for CD43 expression, using an anti-CD43 monoclonal antibody, termed anti-Leu 22 (Becton Dickinson, Lincoln Park, NJ) . All CD43-positive HeLa cell clones selected by this method consistently expressed CD43 for the duration of the experiments (>6 mo) .
  • CD43 A notable feature of CD43 is its extensive substitution with negatively charged, sialic acid residues (Remold et al., J . Biol . Chem . 261:7526, 1986; Carlsson et al., J . Biol . Chem . 261:12779, 1986). It has been proposed that these sialic acid residues confer an anti-adhesion function to CD43 by providing a net negative charge to cell surfaces, resulting in repulsion between CD43-positive cells (Brown et al., Nature (London) 289:456-460, 1981) .
  • CD43 Two distinctive features of CD43 are the extensive O-glycosylation and sialylation of its extracellular domain (Remod-O'Donnell et al., J. Biol . Chem . 261:7526- 7530, 1986; Carlsson et al., J. Biol . Chem . 261:12779- 12786, 1986; Pallant et al., Proc . Natl . Acad . Sci . USA 86:1328-1332, 1989; Shelly et al., Proc . Natl . Acad . Sci . USA 86:2819-2823, 1989).
  • the CD43 domain is not only negatively charged but also of sufficient size to physically interfere with the intercellular interaction.
  • the CD43 domain includes the N-terminal 180 amino acids and, more preferably, includes the N-terminal 220-233 amino acids of the CD43 sequence (as described, e.g., in Shelley et al., Proc . Natl . Acad . Sci . USA 86:2819, 1989; Pallant et al., Proc. Natl . Acad . Sci . USA 86:1328, 1989).
  • the cell targeting molecule can be chosen from ligands, receptors, counterreceptors, antibodies, carbohydrates, or any molecule which is capable of specific interaction with a surface molecule on the targeted cell.
  • the cell targeting domain must also be soluble and, in addition, must be of sufficient size and composition to direct specific interaction with its binding partner on the target cell surface.
  • the cell targeting domain preferably includes between the N-terminal 430 and N-terminal 452 amino acids of the ICAM-l sequence described by Staunton et al. (Cell 52:925, 1988);
  • VCAM-1 the cell targeting domain preferably includes between the N-terminal 580 and the N- terminal 606 amino acids of the VCAM-1 sequence described by Osborn et al.
  • CD43:LNF III, CD43:sialyl Lewis x , CD43:ICAM-1, and CD43:VCAM-1 therapeutic proteins are particularly useful for blocking interactions between white blood cells and activated endothelium and are therefore useful for treating or preventing inflammatory disorders, for example, the vasculitis disorders, lupus and rheumatoid arthritis, as well as for suppressing downstream immune responses leading, for example, to organ rejection.
  • CD43:ICAM-l may also be used to disrupt cell-mediated, organ-specific inflammation secondary to virus infection thus could be useful for treating disorders such as viral myocarditis.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Molecular Biology (AREA)
  • Toxicology (AREA)
  • Cell Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
EP93913851A 1992-06-01 1993-05-13 Verhinderung interzellulärer wechselwirkungen mit chimären cd43-molekülen. Withdrawn EP0650367A4 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US89157192A 1992-06-01 1992-06-01
US891571 1992-06-01
PCT/US1993/004517 WO1994000143A1 (en) 1992-06-01 1993-05-13 Blocking intercellular interactions with cd43 chimeric molecules

Publications (2)

Publication Number Publication Date
EP0650367A1 true EP0650367A1 (de) 1995-05-03
EP0650367A4 EP0650367A4 (de) 1998-04-15

Family

ID=25398441

Family Applications (1)

Application Number Title Priority Date Filing Date
EP93913851A Withdrawn EP0650367A4 (de) 1992-06-01 1993-05-13 Verhinderung interzellulärer wechselwirkungen mit chimären cd43-molekülen.

Country Status (3)

Country Link
EP (1) EP0650367A4 (de)
JP (1) JPH07507278A (de)
WO (1) WO1994000143A1 (de)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5646248A (en) 1993-06-08 1997-07-08 La Jolla Cancer Research Foundation E-selection binding soluble lamp-1 polypeptide
US5980034A (en) * 1996-03-11 1999-11-09 Videojet Systems International, Inc. Cross flow nozzle system for an ink jet printer
US7605177B2 (en) 2001-05-24 2009-10-20 Neuren Pharmaceuticals Limited Effects of glycyl-2 methyl prolyl glutamate on neurodegeneration
CN101678116A (zh) * 2006-05-11 2010-03-24 根特大学 通过唾液酸粘附素靶向巨噬细胞
US10611837B2 (en) 2014-04-10 2020-04-07 Seattle Children's Hospital Transgene genetic tags and methods of use
AU2016306209B2 (en) 2015-08-07 2023-07-06 Seattle Children's Hospital (dba Seattle Children's Research Institute) Bispecific CAR T-cells for solid tumor targeting
US11408005B2 (en) 2016-12-12 2022-08-09 Seattle Children's Hospital Chimeric transcription factor variants with augmented sensitivity to drug ligand induction of transgene expression in mammalian cells
EP3573619A4 (de) 2017-01-27 2020-10-28 SignalRX Pharmaceuticals, Inc. Thienopyranone und furanopyranone als kinase-, bromodomänen- und checkpoint-inhibitoren

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE219838T1 (de) * 1989-03-16 2002-07-15 Blood Res Center Verwendung von funktionellen derivaten des interzellulär-adhäsions-moleküls icam-1 in einer antivirus-therapie
WO1992005188A1 (en) * 1990-09-14 1992-04-02 Biogen, Inc. Production of multimeric glycoproteins through chemical coupling

Also Published As

Publication number Publication date
WO1994000143A1 (en) 1994-01-06
JPH07507278A (ja) 1995-08-10
EP0650367A4 (de) 1998-04-15

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