Combined organ and hematopoietic cells for transplantation tolerance of grafts

Patent metadata

Field	Value
Publication number	US-9561253-B2
Application number	US-201414438159-A
Country	US
Kind code	B2
Filing date	Feb 7, 2014
Priority date	Feb 26, 2013
Publication date	Feb 7, 2017
Grant date	Feb 7, 2017

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 maintaining mixed chimerism for at least six months and withdrawal of immunosuppressive drugs without a rejection episode or graft versus host disease (GVHD) in a recipient of a solid human organ transplantation, wherein a donor of the solid human organ and the recipient are HLA-matched, the method comprising:
administering a pharmaceutically effective dosage of an engineered hematopoietic cell composition to the recipient, wherein the engineered hematopoietic cell composition comprises:
greater than 5×10 5 purified CD34 + cells/kilogram recipient weight and from about 1.5×10 5 to about 1×10 10 CD3 + T cells/kilogram recipient weight,
wherein the purified CD34 + cells in the engineered hematopoietic cell composition are purified to a purity of greater than 85%,
wherein a concentration of iron associated with the purified CD34 + cells is higher than the concentration of iron associated with CD34 + cells prior to the purification, and wherein the engineered hematopoietic cell composition comprises a ratio of the CD3 + T cells to the purified CD34 + cells of greater than 0.25.

2. The method of claim 1 , wherein the engineered hematopoietic cell composition comprises less than 1.7×10 7 purified CD34 + cells/kilogram recipient weight.

3. The method of claim 1 , wherein the engineered hematopoietic cell composition comprises between about 5×10 5 to about 1.7×10 7 purified CD34 + cells/kilogram recipient weight.

4. The method of claim 1 , wherein the donor is living or deceased.

5. The method of claim 1 , wherein the engineered hematopoietic composition comprises:
greater than 5×10 5 purified CD34 + cells/kilogram recipient weight and greater than 1×10 6 CD3 + T cells/kilogram recipient weight when the recipient does not have lupus.

6. The method of claim 1 , wherein the engineered hematopoietic cell composition comprises greater than 1×10 6 purified CD34 + cells/kilogram recipient weight and greater than 1×10 6 CD3 + T cells/kilogram recipient weight.

7. The method of claim 1 , wherein the engineered hematopoietic cell composition comprises greater than 4×10 6 purified CD34 + cells/kilogram recipient weight and greater than 1.5×10 6 CD3 + T cells/kilogram recipient weight.

8. The method of claim 1 , wherein the engineered hematopoietic cell composition comprises between about 1×10 6 to about 1.7×10 7 purified CD34 + cells/kilogram recipient weight and greater than 1.5×10 6 CD3 + T cells/kilogram recipient weight.

9. The method of claim 1 , wherein the purified CD34 + cells are purified to a purity of greater than 95%.

10. The method of claim 1 , wherein the engineered hematopoietic cell composition comprises greater than 4×10 6 purified CD34 + cells/kilogram recipient weight and greater than 5×10 6 CD3 + T cells/kilogram recipient weight.

11. The method of claim 1 , wherein the engineered hematopoietic cell composition is formulated to comprise a ratio of the CD3 + T cells to the purified CD34 + cells of greater than 1.

12. The method of claim 1 , wherein the solid human organ is selected from the group consisting of a heart, intestine, liver, lung, pancreas and kidney.

13. The method of claim 1 , wherein HLA-matched comprises HLA-A, HLA-B and HLA-DR being the same between the donor and the recipient.

14. The method of claim 1 , wherein the engineered hematopoietic cell composition comprises less than 1.7×10 7 purified CD34 + cells/kilogram recipient weight and greater than 1×10 6 CD3 + T cells/kilogram recipient weight.

15. The method of claim 1 , wherein the engineered hematopoietic cell composition comprises between about 1×10 6 to about 1.7×10 7 purified CD34 + cells/kilogram recipient weight and greater than 1×10 6 CD3 + T cells/kilogram recipient weight.

16. The method of claim 1 , wherein the engineered hematopoietic cell composition is isolated from the donor of the solid human organ.

17. The method of claim 1 , wherein the mixed chimerism is defined and monitored as having at least 1% and less than 95% of circulating donor hematopoietic cells.

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

• A61P13/12

  of the kidneys · CPC title