WO2004067697B1 - Icos+ suppresser t cells - Google Patents
Icos+ suppresser t cellsInfo
- Publication number
- WO2004067697B1 WO2004067697B1 PCT/BE2004/000017 BE2004000017W WO2004067697B1 WO 2004067697 B1 WO2004067697 B1 WO 2004067697B1 BE 2004000017 W BE2004000017 W BE 2004000017W WO 2004067697 B1 WO2004067697 B1 WO 2004067697B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- cells
- icos
- suppresser
- treatment
- medicament
- Prior art date
Links
- 210000001744 T-lymphocyte Anatomy 0.000 title claims abstract 25
- 230000000735 allogeneic effect Effects 0.000 claims abstract 8
- 101150013553 CD40 gene Proteins 0.000 claims abstract 7
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 claims abstract 7
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 claims abstract 7
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 claims abstract 7
- 210000000612 antigen-presenting cell Anatomy 0.000 claims abstract 7
- 230000000139 costimulatory effect Effects 0.000 claims abstract 4
- 239000003446 ligand Substances 0.000 claims abstract 4
- 230000004940 costimulation Effects 0.000 claims abstract 3
- 230000004913 activation Effects 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims 24
- 239000003814 drug Substances 0.000 claims 9
- 241000124008 Mammalia Species 0.000 claims 4
- 230000028993 immune response Effects 0.000 claims 4
- 238000004519 manufacturing process Methods 0.000 claims 4
- 208000023275 Autoimmune disease Diseases 0.000 claims 3
- 208000035473 Communicable disease Diseases 0.000 claims 3
- 230000005867 T cell response Effects 0.000 claims 3
- 230000001684 chronic effect Effects 0.000 claims 3
- 208000037976 chronic inflammation Diseases 0.000 claims 3
- 208000037893 chronic inflammatory disorder Diseases 0.000 claims 3
- 238000001415 gene therapy Methods 0.000 claims 3
- 210000000056 organ Anatomy 0.000 claims 3
- 230000002265 prevention Effects 0.000 claims 3
- 238000002054 transplantation Methods 0.000 claims 3
- 230000002950 deficient Effects 0.000 claims 2
- 239000013598 vector Substances 0.000 claims 2
- 208000026935 allergic disease Diseases 0.000 claims 1
- 230000000903 blocking effect Effects 0.000 claims 1
- 210000001124 body fluid Anatomy 0.000 claims 1
- 239000010839 body fluid Substances 0.000 claims 1
- 239000012634 fragment Substances 0.000 claims 1
- 239000003550 marker Substances 0.000 claims 1
- 210000004027 cell Anatomy 0.000 abstract 4
- 108010002350 Interleukin-2 Proteins 0.000 abstract 2
- 238000000338 in vitro Methods 0.000 abstract 2
- 108090000695 Cytokines Proteins 0.000 abstract 1
- 102000004127 Cytokines Human genes 0.000 abstract 1
- 108010002616 Interleukin-5 Proteins 0.000 abstract 1
- 230000004075 alteration Effects 0.000 abstract 1
- 210000004369 blood Anatomy 0.000 abstract 1
- 239000008280 blood Substances 0.000 abstract 1
- 230000016396 cytokine production Effects 0.000 abstract 1
- 230000005764 inhibitory process Effects 0.000 abstract 1
- 230000018711 interleukin-13 production Effects 0.000 abstract 1
- 230000003704 interleukin-23 production Effects 0.000 abstract 1
- 230000022023 interleukin-5 production Effects 0.000 abstract 1
- 230000005923 long-lasting effect Effects 0.000 abstract 1
- 230000001404 mediated effect Effects 0.000 abstract 1
- 108020004999 messenger RNA Proteins 0.000 abstract 1
- 230000002062 proliferating effect Effects 0.000 abstract 1
- 230000035755 proliferation Effects 0.000 abstract 1
- 210000003289 regulatory T cell Anatomy 0.000 abstract 1
- 230000000638 stimulation Effects 0.000 abstract 1
- 230000001629 suppression Effects 0.000 abstract 1
- 230000035897 transcription Effects 0.000 abstract 1
- 238000013518 transcription Methods 0.000 abstract 1
Classifications
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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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0636—T lymphocytes
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4611—T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/462—Cellular immunotherapy characterized by the effect or the function of the cells
- A61K39/4621—Cellular immunotherapy characterized by the effect or the function of the cells immunosuppressive or immunotolerising
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/46433—Antigens related to auto-immune diseases; Preparations to induce self-tolerance
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/46434—Antigens related to induction of tolerance to non-self
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K2035/122—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells for inducing tolerance or supression of immune responses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K2035/124—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells the cells being hematopoietic, bone marrow derived or blood cells
-
- 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/50—Cell markers; Cell surface determinants
- C12N2501/51—B7 molecules, e.g. CD80, CD86, CD28 (ligand), CD152 (ligand)
-
- 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/50—Cell markers; Cell surface determinants
- C12N2501/52—CD40, CD40-ligand (CD154)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Cell Biology (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Mycology (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Hematology (AREA)
- General Engineering & Computer Science (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Human antigen-presenting cells (APC), on which the costimulatory ligands CD40, CD80 and CD86 are blocked e.g. by antibodies, are unable to fully activate allogeneic T cells in vitro. Instead, they induce a long-lasting functional T cell alteration with lack of IL-2, IL-5 and IL-13 production upon allogeneic restimulation. Present invention demonstrates that despite costimulation blockade during in vitro allogeneic stimulation, a non-proliferating responder T cell subpopulation is activated to express ICOS. Removal of these ICOS-expressing cells restores the capacity of reciprocal ICOS negative cells to proliferate and to produce Th1 and Th2 cytokines after allogeneic restimulation. ICOS+ cells on the other hand are anergic at the level of proliferation and Th1 and Th2 cytokine production. However, these cells can produce IL-10, and they suppress the allogeneic responses of either primed or naive T cells through inhibition of IL-2 mRNA transcription. Suppression is not mediated by IL-10, but depends on cell-cell contact. Thus a subtype of regulatory T cells in human blood can be activated in the absence of costimulatory signals from CD40, CD80 and CD86, and that they can be identified by expression of ICOS after activation.
Claims
23
AMENDED CLAIMS
[Received by the International Bureau on 10 October 2004 (10.10.2004) original claims 1 - 32, replaced by amended claims 1 - 20]
1) A method to generate suppresser T cells, comprising 1) collecting from a body fluid or tissue which comprises T cells, 2) allogeneic activation said T cells under a suppressed costimulation condition or under a costimulation-deficient condition, 3) using ICOS expression as a marker to identify a subpopulation of suppresser T cells and 4) isolating said ICOS+ suppresser cells-
2) The method of the claims 1, further comprising expanding the suppresser T cells to clinically relevant numbers.
3) The method of claim 1 or 2f wherein the T cells are allogeneic activated by co-stimulation- deficient antigen-presenting cells.
4) The method of claim 1 or 2, wherein the allogenic T cells are allogeneic activated by antigen-presenting cells in the absence or substantially reduced costimulatory signals of CD40, CD80 and CD86.
5) The method of claim 1 or 2, wherein the costimulatory signals of CD40, CD80 and CD86 are removed or substantially removed by blocking the CD40, CD80 and CD86 ligands on said antigen-presenting cells.
6) The method of claim 1 or 2, wherein the CD40, CD80 and CD86 ligands on the antigen presenting cells are blocked by antibodies.
7) The method of claim 1 or 2, wherein the CD40, CD80 and CD86 ligands on the antigen presenting cells are blocked by a monoclonal antibody or a Fab or Fab' fragment of an antibody.
8) The method of any of the claims 1 to 7, further comprising incorporating the ICOS+ $uppre$$er T cells in a medicament to treat or prevent an autoimmune disease.
9) The method of any of the claims 1 to 7, further comprismg incorporating the ICOS+ suppresser T cells in a product or a medicament to treat or prevent an immune response after tissue or organ transplantation.
10) The method, of any of the claims 1 to 7, further comprising incorporating the ICOS+ suppresser T cells in a product or a medicament to treat or prevent an immune response after gene therapy.
11) The method of any of the claims 1 to 7, further comprising incorporating the ΪCOS+ suppresser T cells in a product or a medicament for the treatment for the treatment of an allergic response.
12) The method of any of the claims 1 to 7, further comprismg incorporating the ICOS+ suppresser T cells in a product or a medicament for the treatment of chronic inflammatory disease or chronic infectious diseases.
13) The use of ICOS+ suppresser T cells obtainable by a method selected from the group consisting of the methods claims 1 to 7 to manufacture of a medicament for the treatment or prevention of an autoimmune disease.
14) The use of ICOS+ suppresser T cells obtainable by a method selected from the group consisting of the methods claims 1 to 7 to manufacture of a medicament for the treatment or prevention of an immune response after tissue or organ transplantation.
15) The use of ICOS+ suppresser T cells obtainable by a method selected from the group consisting of the methods claims 1 to 7 to manufacture of a medicament for the treatment or prevention of an immune response after gene therapy.
16) The use of ICOS+ suppresser T cells obtainable by a method selected from the group consistmg of the methods claims 1 to 7 to manufacture of a medicament for the treatment of chronic inflammatory disease or chronic infectious diseases,
17) The use of ICOS+ suppresser T cells obtainable by the method of the claims 1 to 7 in a treatment mammal to inhibit T cell response associated with chronic inflammatory disease or chronic infectious diseases.
18) The use of ICOS+ suppresser T cells obtainable by the method of the claims 1 to 7 in a treatment of a mammal to induce tissue or organ transplantation tolerance.
19) The use of ICOS+ suppresser T cells obtainable by the method of the claims 1 to 7 in a treatment of a mammal to inhibit T cell response associated with an autoimmune disease.
25
20) The use of ICOS+ suppresser T cells obtainable by the method of the claims 1 to 7 in a treatment of a mammal to inhibit T cell response against vectors and/or vector products used for gene therapy.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP04706580A EP1590449A2 (en) | 2003-01-30 | 2004-01-30 | Icos+ suppresser t cells |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0302167.2A GB0302167D0 (en) | 2003-01-30 | 2003-01-30 | T cell phenotype |
| GB0302167.2 | 2003-01-30 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| WO2004067697A2 WO2004067697A2 (en) | 2004-08-12 |
| WO2004067697A3 WO2004067697A3 (en) | 2004-09-16 |
| WO2004067697B1 true WO2004067697B1 (en) | 2004-11-18 |
Family
ID=9952134
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/BE2004/000017 WO2004067697A2 (en) | 2003-01-30 | 2004-01-30 | Icos+ suppresser t cells |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP1590449A2 (en) |
| GB (1) | GB0302167D0 (en) |
| WO (1) | WO2004067697A2 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011524741A (en) | 2008-05-27 | 2011-09-08 | 協和発酵キリン株式会社 | Interleukin 10 receptor (IL-10R) antibody and method of use |
| CN113341161A (en) * | 2021-06-10 | 2021-09-03 | 苏州大学附属第一医院 | Application of ICOS/ICOSL in diagnosis and treatment of allergic skin diseases |
| CN113981031A (en) * | 2021-11-01 | 2022-01-28 | 山西中医药大学 | Novel T cell function detection method |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1241249A1 (en) * | 2001-03-12 | 2002-09-18 | Gerold Schuler | CD4+CD25+regulatory T cells from human blood |
| DE60210623T2 (en) * | 2001-05-30 | 2007-02-15 | Fondazione Téléthon | EX-VIVO ISOLATED CD25 + CD4 + T CELLS WITH IMMUNOSUPPRESSIVE ACTIVITY AND ITS APPLICATIONS |
-
2003
- 2003-01-30 GB GBGB0302167.2A patent/GB0302167D0/en not_active Ceased
-
2004
- 2004-01-30 EP EP04706580A patent/EP1590449A2/en not_active Withdrawn
- 2004-01-30 WO PCT/BE2004/000017 patent/WO2004067697A2/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP1590449A2 (en) | 2005-11-02 |
| GB0302167D0 (en) | 2003-03-05 |
| WO2004067697A3 (en) | 2004-09-16 |
| WO2004067697A2 (en) | 2004-08-12 |
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