SUPPRESSOR CELLS FOR PREVENTION AND TREATMENT OF IMMUNE RESPONSES IN TRANSPLANTATION

• US 20020034504A1
• Filed: 10/12/1999
• Published: 03/21/2002
• Est. Priority Date: 10/12/1999
• Status: Active Grant

• Current Assignee: Mesoblast International Srl
• Original Assignee: Osiris Therapeutics Incorporated (Smith & Nephew PLC)
• Inventors: MCINTOSH, KEVIN, KLYUSHNENKOVA, ELENA
• Granted Patent: US 6,685,936 B2
• Time in Patent Office: Days
• US Class Current: 424/93.71
• CPC Class Codes: A61K 2035/122 for inducing tolerance or supression of immune responses
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: A61K 2039/5158 Antigen-pulsed cells, e.g. T-cells
• CPC Class Codes: A61K 2239/38 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 39/001 Preparations to induce tolerance to non-self, e.g. prior to transplantation
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4621 immunosuppressive or immunotolerising
• CPC Class Codes: A61K 39/46434 Antigens related to induction of tolerance to non-self
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C12N 2502/1358 Bone marrow mesenchymal stem cells (BM-MSC)
• CPC Class Codes: C12N 5/0637 Immunosuppressive T lymphocytes, e.g. regulatory T cells or Treg

Abstract

A method of reducing an immune response to a transplant in a recipient by treating said recipient with an amount of suppressor T cells effective to reduce or inhibit host rejection of the transplant. The suppressor T cells can be administered before, at the same time as, or after the transplant. Also disclosed is a method of inducing a reduced immune response against a host by foreign tissue, i.e., graft versus host disease, by treatment with suppressor T cells.

Claims

1. A method for reducing an immune response against an alloantigen, comprising:

contacting immune effector cells with suppressor cells in an amount effective to reduce the immune response.

2. The method of claim 1 wherein the suppressor cells are T-cells.

3. The method of claim 1 wherein the effector cells are T cells.

4. A method of reducing an immune response to a donor transplant, comprising treating the recipient with suppressor T cells in an amount effective to reduce an immune response in the recipient to the transplant.

5. The method of claim 4 wherein the suppressor T cells are autologous to the recipient.

6. The method of claim 4, wherein the transplant is skin.

7. The method of claim 4, wherein the suppressor T cells are administered to the recipient prior to administration of the transplant.

8. The method of claim 4, wherein the suppressor T cells are administered concurrently with administration of the transplant.

9. The method of claim 4, wherein the suppressor T cells are administered as a part of the transplant.

10. The method of claim 4, wherein the suppressor T cells are administered after the transplant.

11. The method of claim 4 wherein the suppressor T cells are administered to the transplant recipient to treat rejection of the transplant by the recipient.

12. The method of claim 4, wherein suppressor T cells are human.

13. The method of claim 4, further comprising administering to the recipient immunosuppressive agents.

14. The method of claim 4 wherein the transplant is a solid organ.

15. The method of claim 14 wherein the solid organ is selected from heart, pancreas, kidney, lung, or liver.

17. The method of claim 16 wherein the suppressor cells are T-cells.

18. The method of claim 16 wherein the donor transplant is bone marrow.

19. The method of claim 16, further comprising administering to the recipient immunosuppressive agents.

16. A method of reducing an immune response caused by a donor transplant, comprising contacting the donor transplant with tissue obtained from the transplant recipient and then contacting the donor transplant with suppressor cells in an amount effective to reduce an immune response against the recipient by the donor transplant.

20. A method of treating a transplant recipient for graft versus host disease, comprising treating the recipient of a donor transplant with suppressor T cells in an amount effective to reduce an immune response against the recipient by the transplant.

21. The method of claim 20, wherein the suppressor T cells are autologous to the recipient.

22. The method of claim 20, further comprising administering to the recipient immunosuppressive agents.

26. The method of claim 25 wherein the immune effector cells are CD8+ cells.

27. The method of claim 26 wherein the CD8+ cells are T-cells.

23. A composition for reducing an adverse immune response against a donor transplant, comprising human suppressor T cells in an amount effective to inhibit or reduce an adverse immune response against a donor transplant, and a pharmaceutical carrier.

24. A composition for reducing an adverse immune response against a graft recipient caused by a graft, comprising human suppressor T cells in an amount effective to reduce the adverse immune response against the graft recipient caused by the graft, and a pharmaceutical carrier.

25. A method of preparing suppressor cells, comprising:

contacting activated immune effector cells with mesenchymal stem cells.