WO1999057266A3 - Immunosuppression by blocking t cell co-stimulation signal 2 (b7/cd28 interaction) - Google Patents

Immunosuppression by blocking t cell co-stimulation signal 2 (b7/cd28 interaction) Download PDF

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Publication number
WO1999057266A3
WO1999057266A3 PCT/GB1999/001350 GB9901350W WO9957266A3 WO 1999057266 A3 WO1999057266 A3 WO 1999057266A3 GB 9901350 W GB9901350 W GB 9901350W WO 9957266 A3 WO9957266 A3 WO 9957266A3
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WO
WIPO (PCT)
Prior art keywords
recipient
cells
cell
interaction
stimulation
Prior art date
Application number
PCT/GB1999/001350
Other languages
French (fr)
Other versions
WO1999057266A2 (en
Inventor
Ian Robert Lechler
Anthony Dorling
Original Assignee
Imp College Innovations Ltd
Ian Robert Lechler
Anthony Dorling
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 Imp College Innovations Ltd, Ian Robert Lechler, Anthony Dorling filed Critical Imp College Innovations Ltd
Priority to NZ507706A priority Critical patent/NZ507706A/en
Priority to AU37213/99A priority patent/AU772239B2/en
Priority to EP99919418A priority patent/EP1073737B1/en
Priority to DE69935318T priority patent/DE69935318T2/en
Priority to JP2000547221A priority patent/JP2002513568A/en
Priority to US09/674,462 priority patent/US7432344B1/en
Priority to CA2326671A priority patent/CA2326671C/en
Publication of WO1999057266A2 publication Critical patent/WO1999057266A2/en
Publication of WO1999057266A3 publication Critical patent/WO1999057266A3/en
Priority to US12/231,608 priority patent/US8097598B2/en
Priority to US13/316,791 priority patent/US9090708B2/en

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    • 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
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027—New or modified breeds of vertebrates
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • 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
    • A61K39/0005—Vertebrate antigens
    • A61K39/001—Preparations to induce tolerance to non-self, e.g. prior to transplantation
    • 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
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
    • 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
    • A61K2039/515—Animal cells
    • A61K2039/5154—Antigen presenting cells [APCs], e.g. dendritic cells or macrophages
    • 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
    • A61K2039/515—Animal cells
    • A61K2039/5156—Animal cells expressing foreign proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Zoology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Cell Biology (AREA)
  • Toxicology (AREA)
  • Engineering & Computer Science (AREA)
  • Environmental Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Transplantation (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Animal Husbandry (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Biotechnology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Devices Affording Protection Of Roads Or Walls For Sound Insulation (AREA)

Abstract

The invention provides means and methods for inhibiting T-cell mediated rejection of a xenotransplanted organ by blocking the delivery of co-stimulatory signal 2 (the B7/CD28 interaction) in order to prevent the activation of xenoreactive T-cells in the recipient. In a first aspect, co-stimulation is prevented by administration to the organ recipient of a soluble form of CTLA-4 from the xenogeneic donor organism. This preferentially binds B7 on the xenograft and blocks the interaction between B7 on the xenogeneic donor cells and CD28 on recipient T-cells. In a second aspect, co-stimulation is antagonised by expressing a ligand for CTLA-4 on the xenogeneic donor cells. This ligand binds to CTLA-4 on activated T-cells of the recipient and antagonises signal 2. In a third aspect, co-stimulation is prevented by expressing recipient organism MHC class II on the surface of the cells of the xenogeneic donor organ. The donor cells are thus able to present xenoantigens to a recipient T-cell in the context of self-MHC class II. If the donor cells do not express B7, or if B7 is blocked, the xenoreactive recipient T-cell becomes anergic.
PCT/GB1999/001350 1998-04-30 1999-04-30 Immunosuppression by blocking t cell co-stimulation signal 2 (b7/cd28 interaction) WO1999057266A2 (en)

Priority Applications (9)

Application Number Priority Date Filing Date Title
NZ507706A NZ507706A (en) 1998-04-30 1999-04-30 Immunosuppression by blocking T cell co-stimulation signal 2 (B7/CD28 interaction)
AU37213/99A AU772239B2 (en) 1998-04-30 1999-04-30 Immunosuppression by blocking T cell co-stimulation signal 2 (B7/CD28 interaction)
EP99919418A EP1073737B1 (en) 1998-04-30 1999-04-30 Immunosuppression by blocking t cell co-stimulation signal 2 (b7/cd28 interaction)
DE69935318T DE69935318T2 (en) 1998-04-30 1999-04-30 IMMUNE RESTRICTION THROUGH BLOCKING OF T-CELL COSTIMULATION SIGNAL 2 (B7 / CD28 INTERACTION)
JP2000547221A JP2002513568A (en) 1998-04-30 1999-04-30 Immunosuppression by blocking T cell costimulatory signal 2 (B7 / CD28 interaction)
US09/674,462 US7432344B1 (en) 1998-04-30 1999-04-30 Porcine CTLA-4 for xenograft-specific immunosuppression
CA2326671A CA2326671C (en) 1998-04-30 1999-04-30 Immunosuppression by blocking t cell co-stimulation signal 2 (b7/cd28 interaction)
US12/231,608 US8097598B2 (en) 1998-04-30 2008-09-04 Porcine CTLA-4 for xenograft-specific immunosuppression
US13/316,791 US9090708B2 (en) 1998-04-30 2011-12-12 Porcine CTLA-4 for xenograft-specific immunosuppression

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB9809280.2A GB9809280D0 (en) 1998-04-30 1998-04-30 Immunosupression
GB9809280.2 1998-04-30

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US09/674,462 A-371-Of-International US7432344B1 (en) 1998-04-30 1999-04-30 Porcine CTLA-4 for xenograft-specific immunosuppression
US12/231,608 Continuation US8097598B2 (en) 1998-04-30 2008-09-04 Porcine CTLA-4 for xenograft-specific immunosuppression

Publications (2)

Publication Number Publication Date
WO1999057266A2 WO1999057266A2 (en) 1999-11-11
WO1999057266A3 true WO1999057266A3 (en) 2000-04-20

Family

ID=10831274

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1999/001350 WO1999057266A2 (en) 1998-04-30 1999-04-30 Immunosuppression by blocking t cell co-stimulation signal 2 (b7/cd28 interaction)

Country Status (11)

Country Link
US (3) US7432344B1 (en)
EP (2) EP1073737B1 (en)
JP (2) JP2002513568A (en)
AT (1) ATE355373T1 (en)
AU (1) AU772239B2 (en)
CA (1) CA2326671C (en)
DE (1) DE69935318T2 (en)
ES (1) ES2284251T3 (en)
GB (1) GB9809280D0 (en)
NZ (2) NZ507706A (en)
WO (1) WO1999057266A2 (en)

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GB9809280D0 (en) * 1998-04-30 1998-07-01 Rpms Technology Ltd Immunosupression
US7030228B1 (en) 1999-11-15 2006-04-18 Miltenyi Biotec Gmbh Antigen-binding fragments specific for dendritic cells, compositions and methods of use thereof antigens recognized thereby and cells obtained thereby
EP1274733A1 (en) * 2000-04-12 2003-01-15 Genetics Institute, Inc. Surface-bound antigen binding portions of antibodies that bind to ctla-4 and cd28 and uses therefor
KR100889887B1 (en) * 2000-05-26 2009-03-24 브리스톨-마이어스스퀴브컴파니 Soluble CTLA4 Mutant Molecules and Uses Thereof
US7094874B2 (en) 2000-05-26 2006-08-22 Bristol-Myers Squibb Co. Soluble CTLA4 mutant molecules
US7754208B2 (en) 2001-01-17 2010-07-13 Trubion Pharmaceuticals, Inc. Binding domain-immunoglobulin fusion proteins
US20030133939A1 (en) 2001-01-17 2003-07-17 Genecraft, Inc. Binding domain-immunoglobulin fusion proteins
CN1911965B (en) * 2001-01-17 2013-05-29 新兴产品开发西雅图有限公司 Binding domain-immunoglobulin fusion proteins
ITRM20010408A1 (en) 2001-07-10 2003-01-10 Univ Napoli Federico Ii CYTOTOXIC HUMAN MINI-ANTIBODY FOR CANCER CELLS THAT EXPRESS THE ERBB2 RECEPTOR.
US7601351B1 (en) 2002-06-26 2009-10-13 Human Genome Sciences, Inc. Antibodies against protective antigen
EP1539235A2 (en) 2002-07-01 2005-06-15 Human Genome Sciences, Inc. Antibodies that specifically bind to reg iv
WO2005009134A1 (en) 2003-07-21 2005-02-03 Lifecell Corporation ACELLULAR TISSUE MATRICES MADE FROM GALACTOSE α-1,3-GALACTOSE-DEFICIENT TISSUE
KR20070002057A (en) 2004-03-17 2007-01-04 레비비코르 인코포레이션 Tissue products derived from animals lacking any expression of functional alpha 1,3 galactosyltransferase
CA3079874C (en) 2004-10-22 2023-01-03 Revivicor, Inc. Ungulates with genetically modified immune systems
UA97469C2 (en) 2005-07-25 2012-02-27 Емерджент Продакт Дівелопмент Сіетл, Елелсі Humanized cd37-specific binding immunoglobulin molecule
AU2006292827B2 (en) 2005-08-09 2013-02-14 Revivicor, Inc. Transgenic ungulates expressing CTLA4-IG and uses thereof
NZ573646A (en) 2006-06-12 2012-04-27 Wyeth Llc Single-chain multivalent binding proteins with effector function
NZ603059A (en) 2008-04-11 2014-07-25 Emergent Product Dev Seattle Cd37 immunotherapeutic and combination with bifunctional chemotherapeutic thereof
WO2010051288A1 (en) 2008-10-27 2010-05-06 Revivicor, Inc. Immunocompromised ungulates
EP2464219B1 (en) 2009-08-14 2019-10-23 Revivicor, Inc. Multi-transgenic pigs for diabetes treatment
US9420770B2 (en) 2009-12-01 2016-08-23 Indiana University Research & Technology Corporation Methods of modulating thrombocytopenia and modified transgenic pigs
CN106432474A (en) 2010-03-12 2017-02-22 艾伯维生物医疗股份有限公司 CTLA4 proteins and their uses
ES2680636T3 (en) 2011-02-14 2018-09-10 Revivicor Inc. Genetically modified pigs for xenotransplantation of vascularized xenografts and derivatives thereof
US20140115728A1 (en) 2012-10-24 2014-04-24 A. Joseph Tector Double knockout (gt/cmah-ko) pigs, organs and tissues
US9944689B2 (en) * 2013-03-07 2018-04-17 The General Hospital Corporation Human CTLA4 mutants and use thereof
AU2014341866B2 (en) 2013-11-04 2018-07-05 Lifecell Corporation Methods of removing alpha-galactose
CA2996652A1 (en) * 2015-09-01 2017-03-09 Immunwork Inc. Molecular constructs for preventing the formation of blood clot and/or treating thrombosis
US11352426B2 (en) 2015-09-21 2022-06-07 Aptevo Research And Development Llc CD3 binding polypeptides
CN111214646B (en) * 2019-12-30 2023-08-01 中山大学·深圳 Application of PD-L1/CTLA-4 in preparation of immunosuppressant
JP2023551404A (en) 2020-11-20 2023-12-08 レビビコア， インコーポレイテッド Multiple transgenic pigs with growth hormone receptor knockout for cross-species transplantation
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Citations (1)

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Publication number Priority date Publication date Assignee Title
WO1995034320A2 (en) * 1994-06-07 1995-12-21 Regents Of The University Of Minnesota Methods for inhibiting antigen specific t cell responses

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Publication number Priority date Publication date Assignee Title
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Also Published As

Publication number Publication date
CA2326671A1 (en) 1999-11-11
JP2002513568A (en) 2002-05-14
AU772239B2 (en) 2004-04-22
EP1854884A2 (en) 2007-11-14
ES2284251T3 (en) 2007-11-01
US20100146648A1 (en) 2010-06-10
EP1854884A3 (en) 2009-07-29
DE69935318T2 (en) 2007-11-15
US7432344B1 (en) 2008-10-07
JP2011144205A (en) 2011-07-28
EP1073737A2 (en) 2001-02-07
WO1999057266A2 (en) 1999-11-11
US20130078266A1 (en) 2013-03-28
NZ527297A (en) 2004-12-24
ATE355373T1 (en) 2006-03-15
JP5706225B2 (en) 2015-04-22
CA2326671C (en) 2015-12-15
AU3721399A (en) 1999-11-23
GB9809280D0 (en) 1998-07-01
NZ507706A (en) 2004-01-30
EP1073737B1 (en) 2007-02-28
US9090708B2 (en) 2015-07-28
US8097598B2 (en) 2012-01-17
DE69935318D1 (en) 2007-04-12

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