CA2086325A1 - Ligand for cd28 receptor on b cells and methods - Google Patents

Ligand for cd28 receptor on b cells and methods

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Publication number
CA2086325A1
CA2086325A1 CA002086325A CA2086325A CA2086325A1 CA 2086325 A1 CA2086325 A1 CA 2086325A1 CA 002086325 A CA002086325 A CA 002086325A CA 2086325 A CA2086325 A CA 2086325A CA 2086325 A1 CA2086325 A1 CA 2086325A1
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Prior art keywords
amino acid
receptor
acid sequence
antigen
ligand
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CA002086325A
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French (fr)
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CA2086325C (en
Inventor
Peter S. Linsley
Jeffrey A. Ledbetter
Nitin K. Damle
William Brady
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Bristol Myers Squibb Co
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Individual
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Expired - Lifetime legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], 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
    • C07K16/2827—Immunoglobulins [IGs], 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 against B7 molecules, e.g. CD80, CD86
    • 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
    • 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
    • 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
    • C07K14/70521—CD28, CD152
    • 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
    • C07K14/70532—B7 molecules, e.g. CD80, CD86
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], 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
    • C07K16/2818—Immunoglobulins [IGs], 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 against CD28 or CD152
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56966—Animal cells
    • G01N33/56972—White blood cells
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/32—Fusion polypeptide fusions with soluble part of a cell surface receptor, "decoy receptors"
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
    • C07K2319/75—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor containing a fusion for activation of a cell surface receptor, e.g. thrombopoeitin, NPY and other peptide hormones

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Cell Biology (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Urology & Nephrology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Microbiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Food Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Virology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biotechnology (AREA)
  • Pathology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

2086325 9200092 PCTABS00010 The invention identifies the B7 antigen as a ligand that is reactive with the CD28 receptor on T cells. Fragments and derivatives of the B7 antigen and CD28 receptor, including fusion proteins having amino acid sequences corresponding to the extracellular domains of B7 or CD28 joined to amino acid sequences encoding portions of human immunoglobulin C.gamma.1, are described. Methods are provided for using B7 antigen, its fragments and derivatives, and the CD28 receptor, its fragments and derivatives, as well as antibodies and other molecules reactive with B7 antigen and/or the CD28 receptor, to regulate CD28 positive T cell responses, and immune responses mediated by T cells. The invention also includes an assay method for detecting ligands reactive with cellular receptors mediating intercellular adhesion.

Claims (76)

1. A method for regulating functional T cell responses comprising contacting CD28 positive T cells with a ligand for CD28 receptor.
2. The method of claim 1 wherein said ligand is B7 antigen.
3. The method of claim 2 wherein said T cells are contacted with a fragment or derivative of said B7 antigen.
4. The method of claim 3 wherein said fragment or derivative contains at least a portion of the extracellular domain of the B7 antigen.
5. The method of claim 4 wherein said fragment is a polypeptide having an amino acid sequence containing amino acid residues from about position 1 to about position 215 of the amino acid sequence corresponding to the extracellular domain of B7 antigen.
6. The method of claim 4 wherein said derivative comprises a fusion polypeptide having a first amino acid sequence corresponding to the extracellular domain of B7 antigen and a second amino acid sequence corresponding to a moiety that alters the solubility, affinity and/or valency of said B7 antigen for binding to the CD28 receptor.
7. The method of claim 6 wherein said moiety is an immunoglobulin constant region.
8. The method of claim 6 wherein said derivative comprises a fusion polypeptide having a first amino acid sequence containing amino acid residues from about position 1 to about position 215 of the amino acid sequence corresponding to the extracellular domain of B7 antigen and a second amino acid sequence corresponding to the hinge, CH2 and CH3 regions of human immunoglobulin C.gamma.1.
9. The method of claim 1 wherein said B7 antigen is immobilized to crosslink CD28 receptor on said T cells.
10. The method of claim 9 wherein said T cells are reacted with CHO cells expressing B7 antigen.
11. B7Ig fusion protein reactive with the CD28 receptor on T cells comprising a polypeptide having a first amino acid sequence containing amino acid residues from about position 1 to about position 215 of the amino acid sequence encoding the extracellular domain of B7 antigen and a second amino acid sequence corresponding to the hinge, CH2 and CH3 regions of human immunoglobulin C.gamma.1.
12. B7Ig fusion protein corresponding to the amino acid sequence encoded by DNA having ATCC No. 68627.
13. The method of claim l wherein said B7 antigen is administered in vivo and further comprising administrating a cytokine.
14. The method of claim 13 wherein said cytokine is selected from the group consisting of interleukins, interferons, transforming growth factors, tumor necrosis factors and colony stimulating factors.
15. The method of claim 1 further comprising adding anti-CD antibody to co-react with said T cells.
16. The method of claim 15 wherein said anti-CD antibody is anti-CD2 or anti-CD3 monoclonal antibody.
17. The method of claim 1 wherein said T cells are reacted with B cells expressing B7 antigen and said T
cell responses are stimulated.
18. The method of claim 1 wherein said T cells are reacted with the ligand in soluble form and said T cell responses are inhibited.
19. A method for regulating functional T cell responses comprising reacting B7 positive cells with a ligand reactive with B7 antigen.
20. The method of claim 19 wherein said ligand reactive with B7 antigen is soluble and the interaction of said B7 positive cells with said T cells is inhibited.
21. The method of claim 19 wherein said ligand is a Fab fragment of a monoclonal antibody reactive with B7 antigen.
and said T cell responses are inhibited.
22. The method of claim 21 wherein said monoclonal antibody is mAb BB-1.
23. The method of claim 21 wherein said monoclonal antibody is reactive with a fusion protein comprising a polypeptide having a first amino acid sequence containing amino acid residues from about position 1 to about position 215 of the amino acid sequence corresponding to the extracellular domain of B7 antigen and a second amino acid sequence corresponding to the hinge, CH2 and CH3 regions of human immunoglobulin C.gamma.1.
24. The method of claim 23 wherein said fusion protein is B7Ig corresponding to the amino acid sequence encoded by DNA having ATCC No. 68627.
25. A monoclonal antibody reactive with a fusion protein comprising a polypeptide having a first amino acid sequence containing amino acid residues from about position 1 to about position 215 of the amino acid sequence corresponding to the extracellular domain of B7 antigen and a second amino acid sequence corresponding to the hinge, CH2 and CH3 regions of human immunoglobulin C.gamma.1.
26. The method of claim 19 wherein said ligand is CD28 receptor and said T cell responses are inhibited.
27. The method of claim 26 wherein said ligand is a fragment or derivative of CD28 receptor.
28. The method of claim 27 wherein said fragment or derivative contains at least a portion of the extracellular domain of the CD28 receptor.
29. The method of claim 27 wherein said fragment is a polypeptide having an amino acid sequence containing amino acid residues from about position 1 to about position 134 of the amino acid sequence corresponding to the extracellular domain of CD28 receptor.
30. The method of claim 27 wherein said derivative comprises A fusion polypeptide having a first amino acid sequence corresponding to the extracellular domain of CD28 receptor and a second amino acid sequence corresponding to a moiety that alters the solubility, affinity and/or valency of said CD28 receptor for binding to B7 antigen.
31. The method of claim 30 wherein said moiety is an immunoglobulin constant region.
32. The method of claim 27 wherein said derivative is a CD28 fusion protein comprising a polypeptide having a first amino acid sequence containing amino acid residues from about position 1 to about position 134 of the amino acid sequence corresponding to the extracellular domain of CD28 receptor and a second amino acid sequence corresponding to the hinge, CH2 and CH3 regions of human immunoglobulin C.gamma.1.
33. CD28Ig fusion protein reactive with B7 antigen comprising a polypeptide having a first amino acid sequence containing amino acid residues from about position 1 to about position 134 of the amino acid sequence corresponding to the extracellular domain of CD28 receptor and a second amino acid sequence corresponding to the hinge, CH2 and CH3 regions of human immunoglobulin C.gamma.1.
34. CD28Ig fusion protein corresponding to the amino acid sequence encoded by DNA having ATCC No. 68628.
35. A method for inhibiting functional T cell responses comprising contacting CD28 positive T cells with a ligand reactive with CD28 receptor to prevent binding of said receptor to B7 antigen.
36. The method of claim 35 wherein said ligand is an anti-CD28 monoclonal antibody.
37. The method of claim 36 wherein said ligand is a Fab fragment of anti-CD28 monoclonal antibody.
38. The method of claim 36 wherein said antibody is 9.3 monoclonal antibody produced by hybridoma ATCC No.
HB10271.
39. The method of claim 36 wherein said anti-CD28 antibody is reactive with a fusion protein comprising a polypeptide having a first amino acid sequence containing amino acid residues from about position 1 to about position 134 of the amino acid sequence corresponding to the extracellular domain of CD28 receptor and a second amino acid sequence corresponding to the hinge, CH2 and CH3 regions of human immunoglobulin C.gamma.1.
40. The method of claim 39 wherein said fusion protein is CD28Ig fusion protein corresponding to the amino acid sequence encoded by DNA having ATCC No. 62628.
41. The method of claim 35 wherein said ligand reactive with CD28 receptor is B7 antigen or a fragment or derivative of B7 antigen.
42. The method of claim 41 wherein said derivative is a B7Ig fusion protein.
43. A monoclonal antibody reactive with a fusion protein comprising a polypeptide having a first amino acid sequence containing amino acid residues from about position 1 to about position 134 of the amino acid sequence corresponding to the extracellular domain of CD28 receptor and a second amino acid sequence corresponding to the hinge, CH2 and CH3 regions of human immunoglobulin C.gamma.1.
44. The monoclonal antibody of claim 43 reactive with CD28Ig having ATCC No. 68628.
45. A method for regulating the level of cytokines n vivo comprising administering to a subject a ligand reactive with CD28 receptor to bind to said CD28 receptor and inhibit the production of cytokines by said T cells.
46. The method of claim 45 wherein said ligand is B7 antigen.
47. The method of claim 45 wherein said ligand contains a portion of the extracellular domain of the B7 antigen.
48. The method of claim 47 wherein said ligand is a soluble B7Ig fusion protein.
49. The method of claim 48 wherein said B7Ig fusion protein is B7Ig corresponding to the amino acid sequence encoded by DNA having ATCC No. 68627.
50. The method of claim 45 wherein said ligand is a Fab fragment of anti-CD28 monoclonal antibody.
51. The method of claim 45 wherein said cytokines are selected from the group consisting of interleukins, interferons, transforming growth factors, tumor necrosis factor and colony stimulating factors.
52. A method for treating immune system diseases mediated by CD28 positive T cell interactions with B7 positive cells comprising administering to a subject a ligand for CD28 receptor to regulate the functional T
cell response and/or to regulate cytokine levels.
53. The method of claim 52 wherein said ligand is B7 antigen.
54. The method of claim 52 wherein said ligand is soluble B7Ig fusion protein and said functional T cell response is inhibited.
55. The method of claim 52 wherein said ligand is anti-CD28 monoclonal antibody and said functional T cell response is inhibited.
56. The method of claim 52 wherein said ligand aggregates said CD28 receptor and said functional T cell response is stimulated.
57. The method of claim 56 wherein said ligand is immobilized B7 antigen.
58. The method of claim 52 wherein said cytokine is selected from the group consisting of interleukins, interferons, tumor growth factors, tumor necrosis factors and colony stimulating factors.
59. A method for treating cancer associated with expression of B7 antigen in vivo comprising administering to a subject ligand reactive with B7 antigen.
60. The method of claim 59 wherein said ligand is selected from the group consisting of anti-B7 monoclonal antibody, CD28 antigen and CD28Ig fusion protein.
61. The method of claim 59 wherein said cancer is B7 lymphoma.
62. The method of claim 59 wherein said cancer is T cell leukemia.
63. A method for inhibiting T cell proliferation in graft versus host disease comprising contacting T cells with a ligand for CD28 receptor and an immunosuppressant.
64. The method of claim 63 wherein said ligand for CD28 receptor is soluble B7 antigen.
65. The method of claim 63 wherein said ligand for CD28 receptor is soluble B7Ig fusion protein.
66. The method of claim 63 wherein said immunosuppressant is cyclosporine.
67. An assay method to detect a ligand reactive with a target receptor mediating cellular adhesion system comprising:

a) labeling test cells suspected of expressing ligand for a target receptor to form labeled test cells;

b) contacting said labeled test cells with cells expressing target receptor in a medium lacking divalent cations; and WO 92/00092 PCT/US9l/04682 c) determining whether the labeled test cells bind to said cells expressing target receptor, whereby the presence of ligand reactive with said target receptor is detected.
68. The assay method of claim 67 wherein said target receptor is a receptor on lymphocytes.
69. The assay method of claim 68 wherein said target receptor is a receptor on T cells.
70. The assay method of claim 69 wherein the target receptor is CD28 and the ligand is B7 antigen.
71. The assay method of claim 67 wherein said target receptor is a receptor on B cells.
72. The assay method of claim 67 wherein said medium contains a divalent cation depletion reagent selected from the group consisting of EDTA and EGTA.
73. The assay method of claim 72 further comprising the step of fixing said cells expressing target receptor prior to addition of said reagent for depleting divalent cations.
74. The assay method of claim 73 wherein said step of fixing is carried out using paraformaldehyde.
75. The assay method of claim 67 wherein said cells expressing target receptor are grown in a monolayer prior to adding said test cells.
76. The assay method of claim 67 wherein said test cells are B cells and said cells expressing target receptor are chinese hamster ovary cells.
CA2086325A 1990-07-02 1991-07-01 Ligand for cd28 receptor on b cells and methods Expired - Lifetime CA2086325C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US54798090A 1990-07-02 1990-07-02
US547,980 1990-07-02
US72210191A 1991-06-27 1991-06-27
US722,101 1991-06-27
PCT/US1991/004682 WO1992000092A1 (en) 1990-07-02 1991-07-01 Ligand for cd28 receptor on b cells and methods

Publications (2)

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CA2086325A1 true CA2086325A1 (en) 1992-01-03
CA2086325C CA2086325C (en) 2010-10-05

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EP (1) EP0537293A4 (en)
JP (2) JPH06508501A (en)
CA (1) CA2086325C (en)
WO (1) WO1992000092A1 (en)

Families Citing this family (60)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6534055B1 (en) 1988-11-23 2003-03-18 Genetics Institute, Inc. Methods for selectively stimulating proliferation of T cells
US7479269B2 (en) 1988-11-23 2009-01-20 Genetics Institute, Llc Methods for selectively enriching TH1 and TH2 cells
US6905680B2 (en) 1988-11-23 2005-06-14 Genetics Institute, Inc. Methods of treating HIV infected subjects
US6352694B1 (en) 1994-06-03 2002-03-05 Genetics Institute, Inc. Methods for inducing a population of T cells to proliferate using agents which recognize TCR/CD3 and ligands which stimulate an accessory molecule on the surface of the T cells
US5858358A (en) * 1992-04-07 1999-01-12 The United States Of America As Represented By The Secretary Of The Navy Methods for selectively stimulating proliferation of T cells
DE69032484D1 (en) * 1989-10-27 1998-08-20 Arch Dev Corp COMPOSITIONS AND THE USE THEREOF TO PROMOTE IMMUNOPOTENTIATION
US6406696B1 (en) 1989-10-27 2002-06-18 Tolerance Therapeutics, Inc. Methods of stimulating the immune system with anti-CD3 antibodies
WO1992015671A1 (en) * 1991-03-08 1992-09-17 Cytomed, Inc. Soluble cd28 proteins and methods of treatment therewith
US5637481A (en) * 1993-02-01 1997-06-10 Bristol-Myers Squibb Company Expression vectors encoding bispecific fusion proteins and methods of producing biologically active bispecific fusion proteins in a mammalian cell
EP0637963B1 (en) * 1992-04-07 2004-08-04 The Regents of the University of Michigan Cd28 pathway immunoregulation
US5397703A (en) * 1992-07-09 1995-03-14 Cetus Oncology Corporation Method for generation of antibodies to cell surface molecules
EP0945465B1 (en) * 1992-07-09 2006-09-13 Novartis Vaccines and Diagnostics, Inc. Antagonistic monoclonal antibodies to human CD40
US5747034A (en) * 1992-07-09 1998-05-05 Chiron Corporation Methods and materials for the induction of T cell anergy
MX9306147A (en) * 1992-10-02 1994-06-30 Bristol Myers Squibb Co PHARMACEUTICAL COMPOSITION TO INHIBIT THE GROWTH OF TUMOR CELLS.
AU6586494A (en) * 1993-04-14 1994-11-08 United States Of America As Represented By The Secretary Of The Navy, The Transgenic animal model for autoimmune diseases
US6491916B1 (en) 1994-06-01 2002-12-10 Tolerance Therapeutics, Inc. Methods and materials for modulation of the immunosuppresive activity and toxicity of monoclonal antibodies
DE69434342T2 (en) * 1993-06-04 2006-03-16 The United States Of America Represented By The Secretary Of The Navy Method for the selective stimulation of T cell proliferation.
US6084067A (en) 1993-07-26 2000-07-04 Dana-Farber Cancer Institute CTLA4/CD28 ligands and uses therefor
US6824779B1 (en) 1993-07-26 2004-11-30 Dana-Farber Cancer Institute, Inc. Methods for inhibiting the interaction of B7-2 with its natural ligand
JPH0779793A (en) * 1993-09-14 1995-03-28 Sumitomo Electric Ind Ltd Monoclonal antibody against b70 molecule
US6218510B1 (en) 1994-03-02 2001-04-17 Brigham & Woman's Hospital B7-1 and B7-2 polypeptides
EP0749323B1 (en) 1994-03-08 2000-11-29 Dana-Farber Cancer Institute Methods for modulating t cell anergy
DK0758383T3 (en) * 1994-05-06 2007-05-29 Roussy Inst Gustave Soluble polypeptide fractions of the LAG-3 protein; method of manufacture; therapeutic composition; anti-idiotypic antibody
US7175843B2 (en) 1994-06-03 2007-02-13 Genetics Institute, Llc Methods for selectively stimulating proliferation of T cells
CA2204183A1 (en) * 1994-11-01 1996-05-09 Andrew Lawrence Feldhaus Chimeric receptors for the generation of selectively-activatable th-independent cytotoxic t cells
ATE384127T1 (en) 1994-12-02 2008-02-15 Schering Corp CO-STIMULATORY T-CELL SURFACE ANTIGEN SLAM
US5576423A (en) * 1994-12-02 1996-11-19 Schering Corporation Antibodies to the slam protein expressed on activated T cells
US5877021A (en) * 1995-07-07 1999-03-02 Ribozyme Pharmaceuticals, Inc. B7-1 targeted ribozymes
US7041634B2 (en) 1995-09-27 2006-05-09 Emory University Method of inhibiting immune system destruction of transplanted viable cells
EP0892643B2 (en) * 1996-03-20 2009-09-02 Bristol-Myers Squibb Company Methods for inhibiting an immune response by blocking the gp39/cd40 and ctla4/cd28/b7 pathways and compositions for use therewith
GB9607711D0 (en) * 1996-04-13 1996-06-19 Univ Sheffield T-cell dependent vaccine
CA2194814A1 (en) * 1997-01-10 1998-07-10 Terry L. Delovitch Stimulation of protective t cells to prevent autoimmune disease
CN1224712C (en) 1997-06-04 2005-10-26 牛津生物医学（英国）有限公司 Vector
US7279168B2 (en) 1998-05-01 2007-10-09 Texas A & M University System Recombinant virus expressing foreign DNA encoding feline CD86 and uses thereof
US7078512B2 (en) 1998-05-01 2006-07-18 Schering-Plough Animal Health Corporation Nucleic acid encoding feline CD86
DE19905501B4 (en) 1999-02-10 2005-05-19 MediGene AG, Gesellschaft für molekularbiologische Kardiologie und Onkologie A method of producing a recombinant adeno-associated virus, suitable compositions therefor, and use for the manufacture of a medicament
WO2001039722A2 (en) 1999-11-30 2001-06-07 Mayo Foundation For Medical Education And Research B7-h1, a novel immunoregulatory molecule
US7030219B2 (en) 2000-04-28 2006-04-18 Johns Hopkins University B7-DC, Dendritic cell co-stimulatory molecules
US6965018B2 (en) 2000-06-06 2005-11-15 Bristol-Myers Squibb Company Antibodies directed to B7-related polypeptide, BSL-2
EP1717251B1 (en) 2000-10-02 2012-01-18 Novartis Vaccines and Diagnostics, Inc. Therapy for B-cell malignancies using human anti-CD40 antibodies
US20030133939A1 (en) 2001-01-17 2003-07-17 Genecraft, Inc. Binding domain-immunoglobulin fusion proteins
US7829084B2 (en) 2001-01-17 2010-11-09 Trubion Pharmaceuticals, Inc. Binding constructs and methods for use thereof
US7754208B2 (en) 2001-01-17 2010-07-13 Trubion Pharmaceuticals, Inc. Binding domain-immunoglobulin fusion proteins
US7531168B2 (en) 2001-02-16 2009-05-12 Genetics Institute Llc Method for downmodulating immune response in type I diabetes
US7432351B1 (en) 2002-10-04 2008-10-07 Mayo Foundation For Medical Education And Research B7-H1 variants
US7754209B2 (en) 2003-07-26 2010-07-13 Trubion Pharmaceuticals Binding constructs and methods for use thereof
EP3428191A1 (en) 2004-10-06 2019-01-16 Mayo Foundation for Medical Education and Research B7-h1 and pd-1 in treatment of renal cell carcinoma
US8663634B2 (en) 2005-07-11 2014-03-04 Macrogenics, Inc. Methods for the treatment of autoimmune disorders using immunosuppressive monoclonal antibodies with reduced toxicity
UA97469C2 (en) 2005-07-25 2012-02-27 Емерджент Продакт Дівелопмент Сіетл, Елелсі Humanized cd37-specific binding immunoglobulin molecule
NZ573646A (en) 2006-06-12 2012-04-27 Wyeth Llc Single-chain multivalent binding proteins with effector function
SG10201504662WA (en) 2006-06-14 2015-07-30 Macrogenics Inc Methods For The Treatment Of Autoimmune Disorders Using Immunosuppressive Monoclonal Antibodies With Reduced Toxicity
AU2008293885A1 (en) 2007-07-13 2009-03-05 The John Hopkins University B7-DC variants
NZ603059A (en) 2008-04-11 2014-07-25 Emergent Product Dev Seattle Cd37 immunotherapeutic and combination with bifunctional chemotherapeutic thereof
CA2860460A1 (en) * 2012-01-16 2013-07-25 Atox Bio Ltd. Use of synthetic p2ta peptides in the treatment of ongoing bacterial infection and associated inflammation
US9302005B2 (en) 2013-03-14 2016-04-05 Mayo Foundation For Medical Education And Research Methods and materials for treating cancer
EP3470081A1 (en) 2013-10-01 2019-04-17 Mayo Foundation for Medical Education and Research Methods for treating cancer in patients with elevated levels of bim
US10302653B2 (en) 2014-05-22 2019-05-28 Mayo Foundation For Medical Education And Research Distinguishing antagonistic and agonistic anti B7-H1 antibodies
EP3171896A4 (en) 2014-07-23 2018-03-21 Mayo Foundation for Medical Education and Research Targeting dna-pkcs and b7-h1 to treat cancer
US11352426B2 (en) 2015-09-21 2022-06-07 Aptevo Research And Development Llc CD3 binding polypeptides
US10875923B2 (en) 2015-10-30 2020-12-29 Mayo Foundation For Medical Education And Research Antibodies to B7-H1

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL92382A (en) * 1988-11-23 1994-12-29 Univ Michigan Use of a ligand specific for CD28 in the manufacture of medicament
ZA91463B (en) * 1990-01-25 1992-09-30 Bristol Myers Squibb Co Method of activating cytolytic activity of lymphocytes using anti-cd28 antibody
WO1992015671A1 (en) * 1991-03-08 1992-09-17 Cytomed, Inc. Soluble cd28 proteins and methods of treatment therewith

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