Combined organ and hematopoietic cells for transplantation tolerance of grafts

Patent metadata

Field	Value
Publication number	US-10183043-B2
Application number	US-201815914754-A
Country	US
Kind code	B2
Filing date	Mar 7, 2018
Priority date	Feb 26, 2013
Publication date	Jan 22, 2019
Grant date	Jan 22, 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 cellular product for establishing mixed chimerism in a solid organ transplant recipient that is HLA mismatched from the solid organ transplant donor, the product comprising:
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; and
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.

2. The cellular product of claim 1 , comprising at least about 4×10 6 CD34 + solid organ transplant donor derived cells/kg recipient weight.

3. The cellular product of claim 1 , comprising at least about 5×10 7 CD3 + solid organ transplant donor derived cells/kg recipient weight.

4. The cellular product of claim 1 , comprising at least about 4×10 6 CD34 + solid organ transplant donor derived cells/kg recipient weight and at least about 5×10 7 CD3 + solid organ transplant donor derived cells/kg recipient weight.

5. The cellular product of claim 1 , wherein the CD34 + cells and the CD3 + cells are HLA mismatched to the solid organ transplant recipient at least one of six alleles of HLA-A, HLA-B, and HLA-DR.

6. The cellular product of claim 1 , wherein the CD34 + cells and the CD3 + cells are HLA mismatched to the solid organ transplant recipient at all six HLA alleles.

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

8. The cellular product of claim 1 , wherein CD34 + cells and the CD3 + cells are from multiple apheresis products.

9. The cellular product of claim 1 , wherein the solid organ is selected from the group consisting of heart, intestine, liver, lung, pancreas, and kidney.

10. The cellular product of claim 9 , wherein the solid organ is a kidney.

11. A cellular product for establishing mixed chimerism in a solid organ transplant recipient that is HLA mismatched from the solid organ transplant donor, the product comprising:
greater than 5×10 5 CD34 + solid organ transplant donor derived cells/kg recipient weight in a first container, 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; and
greater than 4×10 7 CD3 + solid organ transplant donor derived cells/kg recipient weight in a second container, 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.

12. The cellular product of claim 11 , comprising at least about 4×10 6 CD34 + solid organ transplant donor derived cells/kg recipient weight.

13. The cellular product of claim 11 , comprising at least about 5×10 7 CD3 + solid organ transplant donor derived cells/kg recipient weight.

14. The cellular product of claim 11 , comprising at least about 4×10 6 CD34 + solid organ transplant donor derived cells/kg recipient weight and at least about 5×10 7 CD3 + solid organ transplant donor derived cells/kg recipient weight.

15. The cellular product of claim 11 , wherein the CD34 + cells and the CD3 + cells are HLA mismatched to the solid organ transplant recipient at least one of six alleles of HLA-A, HLA-B, and HLA-DR.

16. The cellular product of claim 11 , wherein the CD34 + cells and the CD3 + cells are HLA mismatched to the solid organ transplant recipient at all six HLA alleles.

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

18. The cellular product of claim 11 , wherein CD34 + cells and the CD3 + cells are from multiple apheresis products.

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

20. The cellular product of claim 19 , wherein the solid organ is a 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

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P37/06

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

• A61P1/04

  for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title