Combined organ and hematopoietic cells for transplantation tolerance of grafts

Patent metadata

Field	Value
Publication number	US-10258648-B2
Application number	US-201816100828-A
Country	US
Kind code	B2
Filing date	Aug 10, 2018
Priority date	Feb 26, 2013
Publication date	Apr 16, 2019
Grant date	Apr 16, 2019

Abstract

Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to a recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.

First claim

What is claimed is:

1. A method for manufacturing a cryopreserved cellular product for establishing mixed chimerism in a solid organ transplant recipient, the method comprising:
obtaining greater than 5×10 5 CD34+ cells/kg recipient weight;
obtaining greater than 1×10 5 CD3+ cells/kg recipient weight;
cryopreserving the greater than 5×10 5 CD34+ cells/kg recipient weight in a first cryopreservation solution comprising DMSO at a substantially neutral pH; and
cryopreserving the greater than 1×10 5 CD3+ in a second cryopreservation solution comprising DMSO at a substantially neutral pH.

2. The method of claim 1 , wherein the CD34+ cells and the CD3+ cells are cryopreserved in separate containers.

3. The method of claim 1 , wherein the CD34+ cells and the CD3+ cells are cryopreserved as a mixture in a common container.

4. The method of claim 1 , wherein at least one of the first cryopreservation solution and the second preservation solution comprises a polymeric carbohydrate.

5. The method of claim 1 , wherein the first cryopreservation solution and the second preservation solution are different.

6. The method of claim 1 , wherein the first cryopreservation solution and the second preservation solution are the same.

7. The method of claim 1 , wherein the CD34+ cells and the CD3+ cells are HLA matched to an HLA type of the solid organ transplant recipient.

8. The method of claim 1 , wherein the CD34+ cells and the CD3+ cells are HLA mismatched to an HLA type of the solid organ transplant recipient.

9. The method of claim 1 , wherein the CD34+ cells and the CD3+ cells are from a donor related to the solid organ transplant recipient.

10. The method of claim 1 , wherein CD34+ cells and the CD3+ cells are from a single apheresis product.

11. A method for manufacturing a cryopreserved cellular product for establishing mixed chimerism in a solid organ transplant recipient that is HLA matched to the solid organ transplant donor, the method comprising:
obtaining greater than 5×10 5 CD34+ cells/kg recipient weight, wherein the solid organ transplant donor's CD34+ cells are of an HLA type that is matched to the solid organ transplant recipient's HLA type;
obtaining a defined amount of about 1×106 CD3+ cells/kg recipient weight, wherein the solid organ transplant donor's CD3+ cells are of an HLA type that is matched to the solid organ transplant recipient's HLA type; and
cryopreserving the greater than 5×10 5 CD34+ cells/kg recipient weight and the defined amount of about 1×106 CD3+ cells/kg recipient weight in a cryopreservation solution comprising DMSO.

12. The method of claim 11 , wherein the CD34+ cells and the CD3+ cells are cryopreserved as a mixture in a common container comprising the cryopreservation solution.

13. The method of claim 11 , wherein the cryopreservation solution comprises a polymeric carbohydrate.

14. The method of claim 11 , wherein the cryopreservation solution comprises less than 10% DMSO.

15. The method of claim 11 , wherein the product is at a substantially neutral pH.

16. The method of claim 11 , wherein the CD34+ cells and the CD3+ cells are HLA matched to the solid organ transplant recipient at all six alleles of HLA-A, HLA-B, and HLA-DR.

17. The method of claim 11 , wherein the CD34+ cells and the CD3+ cells are from a donor related to the solid organ transplant recipient.

18. The method of claim 11 , wherein CD34+ cells and the CD3+ cells are from a single apheresis product.

19. The method of claim 11 , wherein CD34+ cells and the CD3+ cells are from multiple apheresis products.

20. The method of claim 11 , wherein the solid organ is selected from the group consisting of heart, intestine, liver, lung, pancreas, and kidney.

21. A method for manufacturing a cryopreserved cellular product for establishing mixed chimerism in a solid organ transplant recipient that is HLA mismatched from the solid organ transplant donor, the method comprising:
obtaining greater than 5×10 5 CD34+ solid organ transplant donor derived cells/kg recipient weight, wherein the solid organ transplant donor's CD34+ cells are of an HLA type that is mismatched to the solid organ transplant recipient's HLA type;
obtaining greater than 4×10 7 CD3+ solid organ transplant donor derived cells/kg recipient weight, wherein the solid organ transplant donor's CD3+ cells are of an HLA type that is mismatched to the solid organ transplant recipient's HLA type;
cryopreserving the greater than 5×10 5 CD34+ solid organ transplant donor derived cells/kg recipient weight in a first cryopreservation solution comprising DMSO in a first vessel; and
cryopreserving the greater than 4×10 7 CD3+ solid organ transplant donor derived cells/kg recipient weight in a second cryopreservation solution comprising DMSO in a second vessel.

22. The method of claim 21 , wherein at least one of the first cryopreservation solution and the second preservation solution comprises a polymeric carbohydrate.

23. The method of claim 21 , wherein the first cryopreservation solution and the second preservation solution are different.

24. The method of claim 21 , wherein the first cryopreservation solution and the second preservation solution are the same.

25. The method of claim 21 , wherein each of the first cryopreservation solution and the second cryopreservation solution comprises less than 10% DMSO.

26. The method of claim 21 , wherein the CD34+ cells and the CD3+ cells are HLA mismatched to the solid organ transplant recipient at at least one of six alleles of HLA-A, HLA-B, and HLA-DR.

27. The method of claim 1 , wherein the product is at a substantially neutral pH.

28. The method of claim 21 , wherein CD34+ cells and the CD3+ cells are from a single apheresis product.

29. The method of claim 21 , wherein CD34+ cells and the CD3+ cells are from multiple apheresis products.

30. The method of claim 21 , wherein the solid organ is selected from the group consisting of heart, intestine, liver, lung, pancreas, and kidney.

Assignees

• Univ Leland Stanford Junior

Inventors

• Strober Samuel
• Lowsky Robert

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P1/18

  for pancreatic disorders, e.g. pancreatic enzymes · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title