EP1261708A2 - Compositions et methodes destinees au traitement et au diagnostique du cancer de la prostate - Google Patents

Compositions et methodes destinees au traitement et au diagnostique du cancer de la prostate

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Publication number
EP1261708A2
EP1261708A2 EP01906582A EP01906582A EP1261708A2 EP 1261708 A2 EP1261708 A2 EP 1261708A2 EP 01906582 A EP01906582 A EP 01906582A EP 01906582 A EP01906582 A EP 01906582A EP 1261708 A2 EP1261708 A2 EP 1261708A2
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Prior art keywords
seq
sequence
cdna sequence
polypeptide
sequences
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EP01906582A
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German (de)
English (en)
Inventor
Jiangchun Xu
Davin C. Dillon
Jennifer L. Mitcham
Susan L. Harlocker
Yuqiu Jiang
Steven G. Reed
Michael D. Kalos
Gary Richard Fanger
Craig H. Day
Marc W. Retter
John A. Stolk
Yasir A.W. Skeiky
Aijun Wang
Madeleine Joy Meagher
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Corixa Corp
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Corixa Corp
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Publication of EP1261708A2 publication Critical patent/EP1261708A2/fr
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/10—Cellular immunotherapy characterised by the cell type used
    • A61K40/11—T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/30—Cellular immunotherapy characterised by the recombinant expression of specific molecules in the cells of the immune system
    • A61K40/32—T-cell receptors [TCR]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • 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
    • A61K40/4274—Prostate associated antigens e.g. Prostate stem cell antigen [PSCA]; Prostate carcinoma tumor antigen [PCTA]; Prostatic acid phosphatase [PAP]; Prostate-specific G-protein-coupled receptor [PSGR]
    • A61K40/4275—Prostate specific antigen [PSA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424—Serine endopeptidases (3.4.21)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/53—DNA (RNA) vaccination
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
    • C12N2760/00011—Details
    • C12N2760/16011—Orthomyxoviridae
    • C12N2760/16022—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes

Definitions

  • Figure 7 is a Western blot showing the expression of P501S in baculovirus.
  • Figure 10 is a genomic map showing the location of the prostate genes P775P, P704P, B305D, P712P and P774P within the Cat Eye Syndrome region of chromosome 22q 11.2
  • SEQ ID NO: 155 is the determined cDNA sequence for P263
  • SEQ ID NO: 165 is the determined cDNA sequence for PI 95
  • SEQ ID NO: 206 is the determined extended cDNA sequence for 1D-
  • SEQ ID NO: 364 is the determined cDNA sequence for P781P
  • SEQ ID NO: 365 is the determined cDNA sequence for P785P
  • SEQ ID NO: 382 is the determined full-length cDNA sequence for P711P.
  • SEQ ID NO.432 is the cDNA sequence for 22593.
  • SEQ ID NO.433 is the cDNA sequence for 22594.
  • SEQ ID NO:435 is the cDNA sequence for 22596.
  • SEQ ID NO:450 is the cDNA sequence for 23612.
  • SEQ ID NO: 478 is a second predicted amino acid sequence encoded by the sequence of SEQ ID NO: 474.
  • SEQ ID NO: 537 is the predicted amino acid sequence encoded by SEQ ID NO: 535.
  • SEQ ID NO: 538 is the predicted amino acid sequence encoded by SEQ
  • SEQ ID NO: 692 is the amino acid sequence of the construct Ral 2- P775P-ORF3.
  • SEQ ID NO: 693 and 694 are PCR primers.
  • SEQ ID NO: 704 is the determined cDNA sequence for a P71 IP His tag fusion protein.
  • SEQ ID NO: 705 is the amino acid sequence of the M. tuberculosis antigen Ral 2.
  • SEQ ID NO: 773 is the full-length cDNA sequence of P835P.
  • SEQ ID NO: 774 is the cDNA sequence of the previously identified clone FLJ13581.
  • SEQ ID NO: 789 is the full-length amino acid sequence for PIOOOC.
  • SEQ ID NO: 790 is amino acids 1-100 of SEQ ID NO: 789.
  • polypeptide As used herein, the term "polypeptide" " is used in its conventional meaning, i.e., as a sequence of amino acids.
  • the polypeptides are not limited to a specific length of the product; thus, peptides, oligopeptides, and proteins are included within the definition of polypeptide, and such terms may be used interchangeably herein unless specifically indicated otherwise.
  • This term also does not refer to or exclude post- expression modifications of the polypeptide, for example, glycosylations, acetylations, phosphorylations and the like, as well as other modifications known in the art, both naturally occurring and non-naturally occurring.
  • a polypeptide may be an entire protein, or a subsequence thereof.
  • antisera and antibodies are "antigen-specific” if they specifically bind to an antigen (i.e., they react with the protein in an ELISA or other immunoassay, and do not react detectably with unrelated proteins).
  • antisera and antibodies may be prepared as described herein, and using well-known techniques.
  • a polypeptide "variant,” as the term is used herein, is a polypeptide that typically differs from a polypeptide specifically disclosed herein in one or more substitutions, deletions, additions and/or insertions. Such variants may be naturally occurring or may be synthetically generated, for example, by modifying one or more of the above polypeptide sequences of the invention and evaluating their immunogenic activity as described herein using any of a number of techniques well known in the art.
  • polynucleotide variants will contain one or more substitutions, additions, deletions and/or insertions, preferably such that the immunogenicity of the polypeptide encoded by the variant polynucleotide is not substantially diminished relative to a polypeptide encoded by a polynucleotide sequence specifically set forth herein).
  • variants should also be understood to encompasses homologous genes of xenogenic origin.
  • sequence variants of the selected peptide-encoding DNA segments using site-directed mutagenesis provides a means of producing potentially useful species and is not meant to be limiting as there are other ways in which sequence variants of peptides and the DNA sequences encoding them may be obtained.
  • recombinant vectors encoding the desired peptide sequence may be treated with mutagenic agents, such as hydroxylamine, to obtain sequence variants.
  • mutagenic agents such as hydroxylamine
  • nucleic acid probes to specifically hybridize to a sequence of interest will enable them to be of use in detecting the presence of complementary sequences in a given sample.
  • sequence information for the preparation of mutant species primers, or primers for use in preparing other genetic constructions.
  • ribozymes accelerate phosphoester transfer reactions with a high degree of specificity, often cleaving only one of several phosphoesters in an oligonucleotide substrate (Cech et al, Cell. 1981 Dec;27(3 Pt 2):487-96; Michel and Westhof, J Mol Biol. 1990 Dec 5;216(3):585-610; Reinhold-Hurek and Shub, Nature. 1992 May 14;357(6374): 173-6).
  • This specificity has been attributed to the requirement that the substrate bind via specific base-pairing interactions to the internal guide sequence ("IGS") of the ribozyme prior to chemical reaction.
  • IGS internal guide sequence
  • enzymatic nucleic acids act by first binding to a target RNA. Such binding occurs through the target binding portion of a enzymatic nucleic acid which is held in close proximity to an enzymatic portion of the molecule that acts to cleave the target RNA. Thus, the enzymatic nucleic acid first recognizes and then binds a target RNA through complementary base-pairing, and once bound to the correct site, acts enzymatically to cut the target RNA.
  • Ribozymes may be administered to cells by a variety of methods known to those familiar to the art, including, but not restricted to, encapsulation in liposomes, by iontophoresis, or by incorporation into other vehicles, such as hydrogels, cyclodextrins, biodegradable nanocapsules, and bioadhesive microspheres.
  • ribozymes may be directly delivered ex vivo to cells or tissues with or without the aforementioned vehicles.
  • PNAs peptide nucleic acids compositions.
  • PNA is a DNA mimic in which the nucleobases are attached to a pseudopeptide backbone (Good and Nielsen, Antisense Nucleic Acid Drag Dev. 1997 7(4) 431-37).
  • PNA is able to be utilized in a number methods that traditionally have used RNA or DNA. Often PNA sequences perform better in techniques than the corresponding RNA or DNA sequences and have utilities that are not inherent to RNA or DNA.
  • a review of PNA including methods of making, characteristics of, and methods of using, is provided by Corey (Trends Biotechnol 1997 Jun;15(6):224-9).
  • the primers will bind to the target and the polymerase will cause the primers to be extended along the target sequence by adding on nucleotides.
  • the extended primers will dissociate from the target to form reaction products, excess primers will bind to the target and to the reaction product and the process is repeated.
  • reverse transcription and PCRTM amplification procedure may be performed in order to quantify the amount of mRNA amplified. Polymerase chain reaction methodologies are well known in the art.
  • polypeptide-encoding nucleotide sequences possessing non-naturally occurring codons For example, codons preferred by a particular prokaryotic or eukaryotic host can be selected to increase the rate of protein expression or to produce a recombinant RNA transcript having desirable properties, such as a half- life which is longer than that of a transcript generated from the naturally occurring sequence.
  • the polynucleotide sequences of the present invention can be engineered using methods generally known in the art in order to alter polypeptide encoding sequences for a variety of reasons, including but not limited to, alterations which modify the cloning, processing, and/or expression of the gene product.
  • host cells that contain and express a desired polynucleotide sequence may be identified by a variety of procedures known to those of skill in the art. These procedures include, but are not limited to, DNA-DNA or DNA- RNA hybridizations and protein bioassay or immunoassay techniques which include, for example, membrane, solution, or chip based technologies for the detection and/or quantification of nucleic acid or protein.
  • a variety of protocols for detecting and measuring the expression of polynucleotide-encoded products, using either polyclonal or monoclonal antibodies specific for the product are known in the art. Examples include enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), and fluorescence activated cell sorting (FACS).
  • ELISA enzyme-linked immunosorbent assay
  • RIA radioimmunoassay
  • FACS fluorescence activated cell sorting
  • purification of soluble proteins include, but are not limited to, metal chelating peptides such as histidine-tryptophan modules that allow purification on immobilized metals, protein A domains that allow purification on immobilized immunoglobulin, and the domain utilized in the FLAGS extension/affinity purification system (Immunex Corp., Seattle, Wash.).
  • metal chelating peptides such as histidine-tryptophan modules that allow purification on immobilized metals
  • protein A domains that allow purification on immobilized immunoglobulin
  • the domain utilized in the FLAGS extension/affinity purification system Immunex Corp., Seattle, Wash.
  • the inclusion of cleavable linker sequences such as those specific for Factor XA or enterokinase (Invitrogen. San Diego, Calif.) between the purification domain and the encoded polypeptide may be used to facilitate purification.
  • a number of therapeutically useful molecules are known in the art which comprise antigen-binding sites that are capable of exhibiting immunological binding properties of an antibody molecule.
  • the proteolytic enzyme papain preferentially cleaves IgG molecules to yield several fragments, two of which (the "F(ab)" fragments) each comprise a covalent heterodimer that includes an intact antigen-binding site.
  • the enzyme pepsin is able to cleave IgG molecules to provide several fragments, including the "F(ab') 2 " fragment which comprises both antigen-binding sites.
  • An "Fv" fragment can be produced by preferential proteolytic cleavage of an IgM, and on rare occasions IgG or IgA immunoglobulin molecule.
  • a polypeptide comprising a single CDR (e.g., a CDR1, CDR2 or CDR3) is referred to herein as a "molecular recognition unit.” Crystallographic analysis of a number of antigen-antibody complexes has demonstrated that the amino acid residues of CDRs form extensive contact with bound antigen, wherein the most extensive antigen contact is with the heavy chain CDR3. Thus, the molecular recognition units are primarily responsible for the specificity of an antigen-binding site.
  • FR set refers to the four flanking amino acid sequences which frame the CDRs of a CDR set of a heavy or light chain V region. Some FR residues may contact bound antigen; however, FRs are primarily responsible for folding the V region into the antigen-binding site, particularly the FR residues directly adjacent to the CDRS. Within FRs, certain amino residues and certain stractural features are very highly conserved. In this regard, all V region sequences contain an internal disulfide loop of around 90 amino acid residues. When the V regions fold into a binding-site, the CDRs are displayed as projecting loop motifs which form an antigen- binding surface.
  • a polynucleotide is administered/delivered as "naked" DNA, for example as described in Ulmer et al., Science 259:1145-1149, 1993 and reviewed by Cohen, Science 259:1691-1692, 1993.
  • the uptake of naked DNA may be increased by coating the DNA onto biodegradable beads, which are efficiently transported into the cells.
  • Effector cells may generally be obtained in sufficient quantities for adoptive immunotherapy by growth in vitro, as described herein.
  • Culture conditions for expanding single antigen-specific effector cells to several billion in number with retention of antigen recognition in vivo are well known in the art.
  • Such in vitro culture conditions typically use intermittent stimulation with antigen, often in the presence of cytokines (such as IL-2) and non-dividing feeder cells.
  • cytokines such as IL-2
  • immunoreactive polypeptides as provided herein may be used to rapidly expand antigen-specific T cell cultures in order to generate a sufficient number of cells for immunotherapy.
  • the contact time is sufficient to achieve a level of binding that is at least about 95% of that achieved at equilibrium between bound and unbound polypeptide.
  • the detection reagent is then incubated with the immobilized antibody- polypeptide complex for an amount of time sufficient to detect the bound polypeptide.
  • T cells may be incubated in vitro for 2-9 days (typically 4 days) at 37°C with polypeptide (e.g., 5 - 25 ⁇ g/ml). It may be desirable to incubate another aliquot of a T cell sample in the absence of tumor polypeptide to serve as a control.
  • activation is preferably detected by evaluating proliferation of the T cells.
  • activation is preferably detected by evaluating cytolytic activity.
  • a level of proliferation that is at least two fold greater and/or a level of cytolytic activity that is at least 20% greater than in disease-free patients indicates the presence of a cancer in the patient.
  • Tracer DNA was mixed with 15 ⁇ l driver DNA and 20 ⁇ l of 2 x hybridization buffer (1.5 M NaCl/10 mM EDTA/50 mM HEPES pH 7.5/0.2% sodium dodecyl sulfate), overlaid with mineral oil, and heat-denatured completely.
  • 2 x hybridization buffer 1.5 M NaCl/10 mM EDTA/50 mM HEPES pH 7.5/0.2% sodium dodecyl sulfate
  • the sample was immediately transferred into a 68 °C water bath and incubated for 20 hours (long hybridization [LH]).
  • the reaction mixture was then subjected to a streptavidin treatment followed by phenol/chloroform extraction. This process was repeated three more times.
  • cDNA library subtraction was performed by subtracting the prostate tumor cDNA library described above with the normal pancreas cDNA library and with the three most abundant genes in the previously subtracted prostate tumor specific cDNA library: human glandular kallikrein, prostate specific antigen (PSA), and mitochondria cytochrome C oxidase subunit II. Specifically, 1 ⁇ g each of human glandular kallikrein, PSA and mitochondria cytochrome C oxidase subunit II cDNAs in pCDNA3.1 were added to the driver DNA and subtraction was performed as described above to provide a second subtracted cDNA library hereinafter referred to as the "subtracted prostate tumor specific cDNA library with spike".
  • mRNA was extracted from the tissue sample to be tested, reverse transcribed, and fluorescent-labeled cDNA probes were generated.
  • the microarrays were probed with the labeled cDNA probes, the slides scanned and fluorescence intensity was measured. This intensity correlates with the hybridization intensity.
  • Two clones (referred to as P509S and P510S) were found to be over- expressed in prostate tumor and normal prostate and expressed at low levels in all other normal tissues tested (liver, pancreas, skin, bone marrow, brain, breast, adrenal gland, bladder, testes, salivary gland, large intestine, kidney, ovary, lung, spinal cord, skeletal muscle and colon).
  • the determined cDNA sequences for P509S and P510S are provided in SEQ ID NO: 223 and 224, respectively. Comparison of these sequences with those in the gene bank as described above, revealed some homology to previously identified ESTs.
  • Ll-12 (P501S) was found to be over-expressed in normal prostate and prostate tumor, with some expression being detected in normal skeletal muscle.
  • Jl-12 and Fl-12 (P504S) were found to be over-expressed in prostate tumor, with expression being lower or undetectable in all other tissues tested.
  • the detennined DNA sequences for 10-d8, 10-hlO, 1 l-c8, 8-d4, 8- d9, 8-hl l, 9-fl2 and 9-f3 are provided in SEQ ID NO: 207, 208, 209, 216, 217, 220, 221 and 222, respectively.
  • the predicted amino acid sequences encoded by 5 open reading frames located within SEQ ID NO: 737 are provided in SEQ ID NO: 740-744, with the predicted amino acid sequences encoded by the clone of SEQ ID NO: 738 and 739 being provided in SEQ ID NO: 745-750.
  • DC dendritic cells
  • monocyte cultures derived from PBMC of normal donors by growth for five days in RPMI medium containing 10% human seram, 50 ng/ml GMCSF and 30 ng/ml IL-4.
  • DC were infected overnight with recombinant P501S-expressing vaccinia virus at an M.O.I, of 5 and matured for 8 hours by the addition of 2 micrograms/ml CD40 ligand.
  • Virus was inactivated by UV irradiation, CD8 + cells were isolated by positive selection using magnetic beads, and priming cultures were initiated in 24-well plates.
  • HLA-A2Kb transgenic mice were immunized subcutaneously in the footpad with 100 ⁇ g of p5 peptide together with 140 ⁇ g of hepatitis B viras core peptide (a Th peptide) in Freund's incomplete adjuvant.
  • spleen cells from immunized mice were stimulated in vitro with peptide-pulsed LPS blasts.
  • CTL activity was assessed by chromium release assay five days after primary in vitro stimulation.
  • Retrovirally transduced cells expressing the control antigen P703P and HLA-A2Kb were used as targets. CTL lines that specifically recognized both p5-pulsed targets as well as P703P-expressing targets were identified.
  • each of the HLA B and C alleles were cloned from the donor used in the in vitro priming experiment. Sequence analysis indicated that the relevant alleles were HLA-B8, HLA-B51, HLA-CwOl and HLA- Cw07. Each of these alleles were subcloned into an expression vector and co- transfected together with the P501S gene into VA-13 cells. Transfected VA-13 cells were then tested for the ability to specifically stimulate the P501 S-specific CTL in ELISPOT assays.
  • peptides were combined into pools of 4 peptides, pulsed at 4 ⁇ g/ml onto dendritic cells (DC) for 24 hours, with TNF-alpha. DC were then washed and mixed with negatively selected CD4+ T cells in 96 well U-bottom plates. Cultures were re- stimulated weekly on fresh DC loaded with peptide pools. Following a total of 4 stimulation cycles, cells were rested for an additional week and tested for specificity to
  • a human prostate tumor cDNA expression library as described above was screened using microarray analysis to identify clones that display at least a three fold over-expression in prostate tumor and/or normal prostate tissue, as compared to non-prostate normal tissues (not including testis). 372 clones were identified, and 319 were successfully sequenced. Table I presents a summary of these clones, which are shown in SEQ ID NOs:385-400. Of these sequences SEQ ID NOs:386, 389, 390 and 392 conespond to novel genes, and SEQ ID NOs: 393 and 396 correspond to previously identified sequences. The others (SEQ ID NOs:385, 387, 388, 391, 394, 395 and 397- 400) conespond to known sequences, as shown in Table I.
  • High density lipoprotein binding protein showed 28.06 fold over-expression in prostate tissues as compared to other normal tissues tested. It was over-expressed in 97% of prostate tumors, 75% of normal prostate, and is undetectable in all other normal tissues tested.
  • CGI-69 showed 3.56 fold over-expression in prostate tissues as compared to other normal tissues tested. It is a low abundant gene, detected in more than 90% of prostate tumors, and in 75% normal prostate tissues. The expression of this gene in normal tissues was very low.
  • KIAA0122 showed 4.24 fold over-expression in prostate tissues as compared to other normal tissues tested. It was over-expressed in 57% of prostate tumors, it was undetectable in all normal tissues tested including normal prostate tissues.
  • P501S DNA was used to perform PCR using the primers AW025 (SEQ ID NO: 485) and AW003 (SEQ ID NO: 486).
  • AW025 is a sense cloning primer that contains a Hindlll site.
  • AW003 is an antisense cloning primer that contains an EcoRI site.
  • the fusion constract was transformed into BL21(DE3)pLysE, pLysS and CodonPlus E. coli (Stratagene) and grown overnight in LB broth with kanamycin. The resulting culture was induced with IPTG. Protein was transferred to PVDF membrane and blocked with 5% non-fat milk (in PBS-Tween buffer), washed three times and incubated with mouse anti-His tag antibody (Clontech) for 1 hour. The membrane was washed 3 times and probed with HRP-Protein A (Zymed) for 30 min. Finally, the membrane was washed 3 times and developed with ECL (Amersham). No expression was detected by Western blot. Similarly, no expression was detected by Western blot when the Ral2-P501S-F fusion was used for expression in BL21 CodonPlus by CE6 phage (Invitrogen).
  • a monoclonal hybridoma referred to as 10E3 was chosen for further subcloning.
  • a number of subclones were generated, tested for specific reactivity to P501S using ELISA and typed for IgG isotype. The results of this analysis are shown below in Table V.
  • the monoclonal antibody 10E3-G4-D3 was selected for further study.
  • Immunohistochemical analysis was performed on prostate tumor and a panel of normal tissue sections (prostate, adrenal, breast, cervix, colon, duodenum, gall bladder, ileum, kidney, ovary, pancreas, parotid gland, skeletal muscle, spleen and testis). Tissue samples were fixed in formalin solution for 24 hours and embedded in paraffin before being sliced into 10 micron sections. Tissue sections were permeabihzed and incubated with 10E3-G4-D3 antibody for 1 hr. HRP-labeled anti- mouse followed by incubation with DAB chromogen was used to visualize P501S immunoreactivity.

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Abstract

L'invention concerne des compositions et des méthodes destinées au traitement et au diagnostique de cancer, plus précisément le cancer de la prostate. Ces compositions comprennent un ou plusieurs polypeptides spécifiques de la prostate, des portions immunogéniques de ces polypeptides, des polynucléotides codant pour ces polypeptides, une cellule présentant un antigène qui exprime ces polypeptides, et des cellules T qui sont spécifiques des cellules exprimant ces polypetides. Les compositions selon l'invention conviennent, par exemple, pour le diagnostique, la prévention et/ou le traitement de maladies, notamment le cancer de la prostate.
EP01906582A 2000-01-14 2001-01-16 Compositions et methodes destinees au traitement et au diagnostique du cancer de la prostate Withdrawn EP1261708A2 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021088730A1 (fr) * 2019-11-06 2021-05-14 北京九强生物技术股份有限公司 Kit de mesure d'antigène spécifique de prostate libre et son procédé de préparation

Families Citing this family (64)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030125536A1 (en) * 1996-01-11 2003-07-03 Corixa Corporation Compositions and methods for the therapy and diagnosis of breast cancer
US6828431B1 (en) 1999-04-09 2004-12-07 Corixa Corporation Compositions and methods for the therapy and diagnosis of breast cancer
US7241876B2 (en) 1996-01-11 2007-07-10 Corixa Corporation Compositions and methods for the therapy and diagnosis of breast cancer
US6465611B1 (en) 1997-02-25 2002-10-15 Corixa Corporation Compounds for immunotherapy of prostate cancer and methods for their use
US7033827B2 (en) 1997-02-25 2006-04-25 Corixa Corporation Prostate-specific polynucleotide compositions
US6759515B1 (en) 1997-02-25 2004-07-06 Corixa Corporation Compositions and methods for the therapy and diagnosis of prostate cancer
US20030185830A1 (en) * 1997-02-25 2003-10-02 Corixa Corporation Compositions and methods for the therapy and diagnosis of prostate cancer
US6800746B2 (en) 1997-02-25 2004-10-05 Corixa Corporation Compositions and methods for the therapy and diagnosis of prostate cancer
US6329505B1 (en) 1997-02-25 2001-12-11 Corixa Corporation Compositions and methods for therapy and diagnosis of prostate cancer
US6818751B1 (en) 1997-08-01 2004-11-16 Corixa Corporation Compositions and methods for the therapy and diagnosis of prostate cancer
US7517952B1 (en) 1997-02-25 2009-04-14 Corixa Corporation Compositions and methods for the therapy and diagnosis of prostate cancer
US6894146B1 (en) 1997-02-25 2005-05-17 Corixa Corporation Compositions and methods for the therapy and diagnosis of prostate cancer
US7202342B1 (en) 1999-11-12 2007-04-10 Corixa Corporation Compositions and methods for the therapy and diagnosis of prostate cancer
US6630305B1 (en) 1999-11-12 2003-10-07 Corixa Corporation Compositions and methods for the therapy and diagnosis of prostate cancer
US6620922B1 (en) 1997-02-25 2003-09-16 Corixa Corporation Compositions and methods for the therapy and diagnosis of prostate cancer
US6943236B2 (en) 1997-02-25 2005-09-13 Corixa Corporation Compositions and methods for the therapy and diagnosis of prostate cancer
US6613872B1 (en) 1997-02-25 2003-09-02 Corixa Corporation Compounds for immunotherapy of prostate cancer and methods for their use
AU7019498A (en) 1997-04-10 1998-10-30 Diagnocure Inc. Pca3, pca3 genes, and methods of use
US6861215B1 (en) 1998-05-21 2005-03-01 Diadexus, Inc. Method of diagnosing, monitoring, and staging prostate cancer
DE69941187D1 (de) 1998-06-01 2009-09-10 Agensys Inc Serpentintransmembranantigene exprimiert in menschlichem krebs und deren verwendungen
US7037667B1 (en) 1998-06-01 2006-05-02 Agensys, Inc. Tumor antigen useful in diagnosis and therapy of prostate and colon cancer
US6833438B1 (en) 1999-06-01 2004-12-21 Agensys, Inc. Serpentine transmembrane antigens expressed in human cancers and uses thereof
US20030149531A1 (en) 2000-12-06 2003-08-07 Hubert Rene S. Serpentine transmembrane antigens expressed in human cancers and uses thereof
US6902892B1 (en) 1998-10-19 2005-06-07 Diadexus, Inc. Method of diagnosing, monitoring, staging, imaging and treating prostate cancer
US7022497B1 (en) 1999-03-11 2006-04-04 Mt. Sinai Hospital Human kallikrein-like genes
US6943235B1 (en) 1999-04-12 2005-09-13 Agensys, Inc. Transmembrane protein expressed in prostate cancer
DK1222266T3 (da) 1999-09-29 2006-07-10 Diagnocure Inc PCA3-messenger-RNA i benigne og maligne prostatavæv
US6790631B1 (en) 1999-10-05 2004-09-14 Agensys, Inc. G protein-coupled receptor up-regulated in prostate cancer and uses thereof
US7361338B2 (en) 1999-10-05 2008-04-22 Agensys, Inc. Methods to inhibit growth of prostate cancer cells
EP1517913B9 (fr) * 1999-10-07 2007-08-29 Corixa Corporation Une sequence codante de mycobacterium tuberculosis pour favoriser une expression de proteines heterologues
US20020048777A1 (en) 1999-12-06 2002-04-25 Shujath Ali Method of diagnosing monitoring, staging, imaging and treating prostate cancer
WO2001073032A2 (fr) * 2000-03-27 2001-10-04 Corixa Corporation Compositions et methodes de therapie et de diagnostic du cancer de la prostate
PT2133100E (pt) 2000-06-20 2012-01-11 Corixa Corp Antigénio mtb32a de mycobacterium tuberculosis com um local activo inactivado e suas proteínas de fusão
AU2001281322A1 (en) * 2000-07-13 2002-01-30 Biogen, Inc. Methods of identifying renal protective factors
WO2002010382A2 (fr) * 2000-07-28 2002-02-07 Ulrich Wissenbach Marqueurs trp8, trp9 et trp10 associes au cancer
US7048931B1 (en) 2000-11-09 2006-05-23 Corixa Corporation Compositions and methods for the therapy and diagnosis of prostate cancer
EP1573024A4 (fr) 2001-04-10 2007-08-29 Agensys Inc Acides nucleiques et proteines correspondantes utiles pour la detection et le traitement de divers cancers
CA2446788A1 (fr) * 2001-05-09 2002-11-14 Corixa Corporation Compositions et procedes pour la therapie et le diagnostic du cancer de la prostate
US6897024B2 (en) 2001-05-31 2005-05-24 Stichting Katholieke Universiteit More Particularly The University Medical Centre Nijmegen Nucleic acid molecules comprising the promoter for PCA3, and uses thereof
EP1409549A4 (fr) * 2001-06-20 2007-10-24 Genentech Inc Compositions et procedes destines au diagnostic et au traitement de tumeurs
US20050272120A1 (en) 2001-06-20 2005-12-08 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
WO2003022995A2 (fr) * 2001-09-06 2003-03-20 Agensys, Inc. Acide nucleique et proteine correspondante designes par steap-1 utiles dans le traitement et la detection du cancer
US7494646B2 (en) 2001-09-06 2009-02-24 Agensys, Inc. Antibodies and molecules derived therefrom that bind to STEAP-1 proteins
AU2003210663A1 (en) 2002-01-25 2003-09-02 The Regents Of The University Of California Methods of modulating cold sensory perception
DE10215321A1 (de) * 2002-04-02 2003-10-23 Metagen Pharmaceuticals Gmbh Trp-p8 Splice Varianten und regulatorische RNA
RU2004135541A (ru) * 2002-06-11 2005-10-10 ГлаксоСмитКлайн Байолоджикалз с.а. (BE) Иммуногенные композиции
DE10234901A1 (de) * 2002-07-26 2004-02-12 Metagen Pharmaceuticals Gmbh Verwendung von am Mrp4 bindenden Substanzen zur Diagnose und Behandlung von Krebserkrankungen
US20040081653A1 (en) 2002-08-16 2004-04-29 Raitano Arthur B. Nucleic acids and corresponding proteins entitled 251P5G2 useful in treatment and detection of cancer
JP4824540B2 (ja) 2003-02-07 2011-11-30 ダイアノキュアー インク． サンプル中の前立腺癌を検出する方法
BRPI0418766B8 (pt) 2004-04-22 2021-05-25 Agensys Inc anticorpo ou seu fragmento, vetor, composição farmacêutica, ensaio e método para detectar a presença de proteína steap-1, bem como método para distribuir um agente citotóxico ou um agente de diagnóstico
CA2491067A1 (fr) 2004-12-24 2006-06-24 Stichting Katholieke Universiteit Rapport entre arnm dans les sediments urinaires ou l'urine en tant que marqueur pronostique du cancer de la prostate
JP4969444B2 (ja) * 2005-06-14 2012-07-04 ディナベック株式会社 抗体の作製方法
PT2845866T (pt) 2006-10-27 2017-08-09 Genentech Inc Anticorpos e imunoconjugados e utilizações dos mesmos
SG10201806573TA (en) * 2012-05-25 2018-09-27 Cellectis Methods for engineering allogeneic and immunosuppressive resistant t cell for immunotherapy
CN104357451B (zh) * 2014-12-02 2016-09-21 广州市番禺区中心医院 针对dd3基因的小干扰rna及其表达载体构建与应用
GB201513921D0 (en) * 2015-08-05 2015-09-23 Immatics Biotechnologies Gmbh Novel peptides and combination of peptides for use in immunotherapy against prostate cancer and other cancers
GB201520566D0 (en) * 2015-11-23 2016-01-06 Immunocore Ltd & Adaptimmune Ltd Peptides
GB201520568D0 (en) 2015-11-23 2016-01-06 Immunocore Ltd Peptides
GB201520550D0 (en) 2015-11-23 2016-01-06 Immunocore Ltd & Adaptimmune Ltd Peptides
CN110325205B (zh) * 2016-12-22 2023-08-15 库尔生物制药有限公司 T细胞调节性多聚体多肽及其使用方法
PE20200010A1 (es) 2017-04-03 2020-01-06 Hoffmann La Roche Anticuerpos que se unen a steap-1
CA3185241A1 (fr) * 2020-07-13 2022-01-20 Noam LEVIN Recepteurs de lymphocytes t a restriction hla de classe ii diriges contre ras ayant une mutation g12d
JP2024501482A (ja) * 2020-12-14 2024-01-12 ビオンテック ユーエス インコーポレイテッド がん免疫療法のための組織特異的抗原
CN114250238B (zh) * 2021-11-26 2023-08-25 北京航空航天大学 基因编码的神经元发育调控多肽及其应用

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CO4600637A1 (es) * 1996-03-15 1998-05-08 Corixa Corp Compuestos para inmunoterapia e inmunodiagnosis del cancer de prostata
EP1005546A2 (fr) * 1997-02-25 2000-06-07 Corixa Corporation Composes permettant l'immunotherapie du cancer de la prostate et procedes concernant leur utilisation
CA2281954A1 (fr) * 1997-02-25 1998-08-27 Corixa Corporation Composes servant au diagnostic immunologique de cancer de la prostate et leurs procedes d'utilisation
TR200100916T2 (fr) * 1998-07-14 2002-06-21 Corixa@@Corporation
WO2001025272A2 (fr) * 1999-10-04 2001-04-12 Corixa Corporation Compositions et methodes de therapie et de diagnostic du cancer de la prostate
AU1656501A (en) * 1999-11-12 2001-06-06 Corixa Corporation Compositions and methods for the therapy and diagnosis of prostate cancer

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
GIRI D. ET AL: "Alterations in the expression of basic Fibroblast Growth Factor (FGF) 2 and its receptor FGFR-1 in human prostate cancer", CLINICAL CANCER RESEARCH, vol. 5, no. 5, May 1999 (1999-05-01), US, pages 1063 - 1071 *
STUBBS A. ET AL: "Differentially expressed genes in hormone refractory prostate cancer", AMERICAN JOURNAL OF PATHOLOGY, vol. 154, no. 4, May 1999 (1999-05-01), US, pages 1335 - 1343 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021088730A1 (fr) * 2019-11-06 2021-05-14 北京九强生物技术股份有限公司 Kit de mesure d'antigène spécifique de prostate libre et son procédé de préparation

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NO20023402D0 (no) 2002-07-15
IL150732A0 (en) 2003-02-12
PL356908A1 (en) 2004-07-12
AU3447401A (en) 2001-07-24
RU2002121771A (ru) 2004-03-10
CA2397741A1 (fr) 2001-07-19
HUP0203968A3 (en) 2004-09-28
MXPA02006934A (es) 2003-01-28
CN1436234A (zh) 2003-08-13
ZA200206400B (en) 2004-01-21
BR0107643A (pt) 2003-06-10
HUP0203968A2 (hu) 2003-03-28
WO2001051633A2 (fr) 2001-07-19
KR20030016217A (ko) 2003-02-26
JP2003528591A (ja) 2003-09-30
CZ20022756A3 (cs) 2003-02-12
WO2001051633A3 (fr) 2002-06-20
WO2001051633A9 (fr) 2002-10-31

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