Suppressor cells induced by culture with mesenchymal stem cells for treatment of immune responses in transplantation

• US 6,685,936 B2
• Filed: 10/12/1999
• Issued: 02/03/2004
• Est. Priority Date: 10/12/1999
• Status: Expired due to Term

• Current Assignee: Mesoblast International Srl
• Original Assignee: Osiris Therapeutics Incorporated (Smith & Nephew PLC)
• Inventors: McIntosh, Kevin, Klyushnenkova, Elena
• Primary Examiner(s): Ewoldt, G. R.
• Application Number:
  US09/415,627
• Publication Number:
  US 20020034504A1
• Time in Patent Office: 1,575 Days
• Field of Search: 424/154.1, 424/93.71, 424/278.1, 435/373
• 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 of reducing an immune response against an alloantigen, comprising:

(a) culturing activated human T-cells with human mesenchymal stem cells in vitro, whereby said human mesenchymal stem cells induce said activated human T-cells to become human suppressor T-cells; and

(b) contacting immune effector cells with said human suppressor T-cells in an amount effective to reduce the immune response.

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

3. A method of treating a transplant recipient for graft versus host disease, comprising:

(a) culturing activated human T-cells with human mesenchymal stem cells in vitro, whereby said human mesenchymal stem cells induce said activated human T-cells to become human suppressor T-cells; and

(b) treating the recipient of a donor transplant with said human suppressor T-cells in an amount effective to reduce an immune response against the recipient by the transplant.

4. The method of claim 3, wherein the human suppressor T-cells are allogeneic to the human mesenchymal stem cells.

5. A method of reducing an immune response to a donor transplant, comprising:

(a) culturing activated human T-cells with human mesenchymal stem cells in vitro to produce human suppressor T-cells; and

(b) administering to the recipient of the donor transplant said human suppressor T-cells in an amount effective to reduce an immune response in the recipient to the transplant.

6. The method of claim 5 wherein the human mesenchymal stem cells are allogeneic to the activated human T-cells.

7. The method of claim 5 wherein the transplant is a skin transplant.

8. The method of claim 5 wherein the human suppressor T-cells are administered to the recipient prior to administration of the transplant.

9. The method of claim 5 wherein the human suppressor T-cells are administered concurrently with administration of the transplant.

10. The method of claim 5 wherein the human suppressor T-cells are administered as part of the transplant.

11. The method of claim 5 wherein the human suppressor T-cells are administered after the transplant.

12. The method of claim 5 wherein the human suppressor T-cells are administered to the transplant recipient to treat rejection of the transplant by the recipient.

13. The method of claim 5 wherein the transplant is a solid organ.

14. The method of claim 5 wherein said solid organ is selected from the group consisting of heart, pancreas, kidney, lung and liver.