Combined organ and hematopoietic cells for transplantation tolerance of grafts

Patent metadata

Field	Value
Publication number	US-11007220-B2
Application number	US-201816199599-A
Country	US
Kind code	B2
Filing date	Nov 26, 2018
Priority date	Feb 26, 2013
Publication date	May 18, 2021
Grant date	May 18, 2021

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 of manufacturing a 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 one or more samples comprising CD34+ cells and CD3+ cells; and
processing the one or more samples to produce a cellular 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 method of claim 1 , wherein the one or more samples are processed such that cellular product comprises at least about 4×10 6 CD34 + solid organ transplant donor derived cells/kg recipient weight.

3. The method of claim 1 , wherein the one or more samples are processed such that cellular product comprises at least about 5×10 7 CD3 + solid organ transplant donor derived cells/kg recipient weight.

4. The method of claim 1 , wherein the one or more samples are processed such that cellular product comprises 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 method 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 method 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 method of claim 1 , wherein CD34 + cells and the CD3 + cells are from a single apheresis product.

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

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

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

11. A method of manufacturing a 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 one or more samples comprising CD34+ cells and CD3+ cells; and
processing the one or more samples to produce a cellular 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 method of claim 11 , wherein the one or more samples are processed such that cellular product comprises at least about 4×10 6 CD34 + solid organ transplant donor derived cells/kg recipient weight.

13. The method of claim 11 , wherein the one or more samples are processed such that cellular product comprises at least about 5×10 7 CD3 + solid organ transplant donor derived cells/kg recipient weight.

14. The method of claim 11 , wherein the one or more samples are processed such that cellular product comprises 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 method 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 method 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 method of claim 11 , wherein CD34 + cells and the CD3 + cells are from a single apheresis product.

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

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

20. The method of claim 19 , wherein the solid organ is a kidney.

Assignees

• Univ Leland Stanford Junior

Inventors

• Strober Samuel
• Lowsky Robert

Classifications

• A61K35/14 Primary

  Blood; Artificial blood (perfluorocarbons A61K31/02; umbilical cord blood A61K35/51; haemoglobin A61K38/42) · CPC title

• A61K40/418

  Antigens related to induction of tolerance to non-self · CPC title

• A61K40/22

  Immunosuppressive or immunotolerising · CPC title

• A61K40/11

  T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells · CPC title

• A61K40/10

  characterised by the cell type used · CPC title