Liver stromal cells for prevention and treatment of immune responses in transplantation

• US 9,408,876 B2
• Filed: 09/08/2005
• Issued: 08/09/2016
• Est. Priority Date: 09/10/2004
• Status: Expired due to Fees

• Current Assignee: Cognate BioServices, Inc.
• Original Assignee: Cognate Therapeutics, Inc.
• Inventors: McIntosh, Kevin R.
• Primary Examiner(s): Kim, Taeyoon
• Assistant Examiner(s): GOUGH, TIFFANY MAUREEN
• Application Number:
  US11/222,316
• Publication Number:
  US 20060057125A1
• Time in Patent Office: 3,988 Days
• Field of Search: 424/93.7
• US Class Current: 1/1
• CPC Class Codes: A61K 2035/122 for inducing tolerance or supression of immune responses
• CPC Class Codes: A61K 35/407 Liver; Hepatocytes
• CPC Class Codes: A61K 39/001 Preparations to induce tolerance to non-self, e.g. prior to transplantation
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C12N 5/067 Hepatocytes

Abstract

The present invention encompasses methods and compositions for reducing an immune response to a transplant in a recipient by treating said recipient with an amount of liver stromal cells effective to reduce or inhibit host rejection of 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 liver stromal cells.

Claims

1. A method of reducing an immune response of effector cells against an alloantigen to the effector cells in a transplant recipient comprising:

administering to the transplant recipient isolated adult liver stromal cells (LSCs) wherein the LSCs are incapable of differentiating into fat cells or bone producing cells, in an amount effective to reduce an immune response of effector cells against an alloantigen to the effector cells, whereby in the transplant recipient the effector cells have a reduced immune response against the alloantigen.

2. The method of claim 1, wherein said effector cells are T cells.

3. The method of claim 2, wherein said T cells are from a donor and the alloantigen is from said recipient.

4. The method of claim 2, wherein said T cells are from said recipient and the alloantigen is from a donor.

5. The method of claim 2, wherein said T cells are present in a transplant.

6. The method of claim 1, wherein the transplant recipient receives a bone marrow transplant.

7. The method of claim 1, wherein the transplant recipient receives a hematopoietic stem cell transplant.

8. The method of claim 1, wherein the transplant recipient receives a neural stem cell transplant.

9. The method of claim 1, wherein prior to said administering to a transplant recipient liver stromal cells, said liver stromal cells have been expanded in culture.

10. The method of claim 1, wherein said effector cells are T cells from a donor previously activated by contacting said T cells with a cell or a tissue from the recipient prior to transplantation in order to activate said T cells, and further wherein said immune response is the reactivation of said T cells.

11. The method of claim 1, wherein the liver stromal cells are administered to the transplant recipient to treat rejection of the transplant by the recipient.

12. The method of claim 1, wherein the liver stromal cells are human liver stromal cells.

13. The method of claim 1, further comprising administering to the recipient an immunosuppressive agent.

14. The method of claim 1, wherein the transplant is a solid organ.

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

16. The method of claim 1, wherein said liver stromal cells are administered to the recipient prior to a transplant.

17. The method of claim 1, wherein said liver stromal stem cells are administered to the recipient concurrently with a transplant.

18. The method of claim 17, wherein said liver stromal cells are administered as part of a transplant.

19. The method of claim 1, wherein the liver stromal cells are administered to the recipient subsequent to the transplantation of a transplant.

20. The method of claim 1, wherein said liver stromal cells are administered intravenously to the recipient.

21. The method of claim 1, wherein said effector cells are cells of a recipient of a donor transplant.

22. The method of claim 1, wherein said liver stromal cells are genetically modified.

23. A method for reducing an immune response of effector cells against an alloantigen to the effector cells in a transplant recipient comprising:

administering to a recipient a transplant treated with isolated adult liver stromal cells (LSCs) wherein the LSCs are incapable of differentiating into fat cells or bone producing cells in an amount effective to reduce an immune response of effector cells against an alloantigen to the effector cells, whereby in the transplant recipient the effector cells have a reduced immune response against the alloantigen.

24. The method of claim 23 wherein said effector cells are T cells.

25. A method of reducing an immune response of effector cells against allogeneic cells, the method comprising treating the effector cells with isolated adult liver stromal cells, (LSCs), wherein the LSCs are incapable of differentiating into fat cells or bone producing cells.

26. The method of claim 25 wherein said effector cells are T cells.