Combined organ and hematopoietic cells for transplantation tolerance of grafts

Patent metadata

Field	Value
Publication number	US-11458165-B2
Application number	US-201916515955-A
Country	US
Kind code	B2
Filing date	Jul 18, 2019
Priority date	Feb 26, 2013
Publication date	Oct 4, 2022
Grant date	Oct 4, 2022

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 establishing mixed chimerism in a solid organ transplant recipient, the method comprising:
providing to the recipient of the solid organ transplant a cellular product comprising greater than 5×10 5 CD34 + cells/kg recipient weight, and greater than 1×10 5 CD3 + cells/kg recipient weight; and
providing to the recipient of the solid organ transplant a cell type that facilitates engraftment of the cells of the cellular product in the bone marrow of the recipient of the solid organ transplant.

2. The method of claim 1 , wherein prior to providing the cellular product and the cell type that facilitates engraftment, the method comprises providing total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) to the recipient of the solid organ transplant.

3. The method of claim 1 , wherein the cellular product comprises at least about 10×10 6 CD34 + cells/kg recipient weight.

4. The method of claim 1 , wherein the cellular product comprises at least about 1×10 7 CD3 + cells/kg recipient weight.

5. The method of claim 1 , wherein the cellular product comprises at least about 10×10 6 CD34 + cells/kg recipient weight and at least about 1×10 7 CD3 + cells/kg recipient weight.

6. The method of claim 1 , wherein the cellular product is substantially devoid of platelets and red blood cells.

7. The method of claim 1 , wherein at least two of the CD34 + cells, the CD3 + cells, and the cell type that facilitates engraftment are provided in separate containers.

8. The method of claim 1 , wherein the CD34 + cells, the CD3 + cells, and the cell type that facilitates engraftment are provided as a mixture in a common container.

9. 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.

10. 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.

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

12. A method for establishing mixed chimerism in a solid organ transplant recipient, the method comprising:
providing to the recipient of the solid organ transplant a cellular product comprising greater than 5×10 5 CD34 + cells/kg recipient weight, and a 10×10 7 CD3+ cells/kg recipient weight, wherein the cellular product is substantially devoid of platelets and red blood cells; and
providing to the recipient of the solid organ transplant a cell type that facilitates engraftment of the cells of the cellular product in the bone marrow of the recipient of the solid organ transplant.

13. The method of claim 12 , wherein prior to providing the cellular product and the cell type that facilitates engraftment, the method comprises providing total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) to the recipient of the solid organ transplant.

14. The method of claim 12 , wherein the cellular product comprises at least about 10×10 6 CD34 + cells/kg recipient weight.

15. The method of claim 12 , wherein the cellular product comprises at least about 10×10 6 CD34 + cells/kg recipient weight and 1×10 7 CD3 + cells/kg recipient weight.

16. The method of claim 12 , wherein at least two of the CD34 + cells, the CD3 + cells, and the cell type that facilitates engraftment are provided in separate containers.

17. The method of claim 12 , wherein the CD34 + cells, the CD3 + cells, and the cell type that facilitates engraftment are provided as a mixture in a common container.

18. The method of claim 12 , wherein the CD34 + cells and the CD3 + cells are HLA matched to an HLA type of the solid organ transplant recipient.

19. The method of claim 12 , wherein the CD34 + cells and the CD3 + cells are HLA mismatched to an HLA type of the solid organ transplant recipient.

20. The method of claim 12 , wherein the CD34 + cells and the CD3 + cells are from a single apheresis product.

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

• A61K2035/124

  the cells being hematopoietic, bone marrow derived or blood cells · CPC title

• A61P13/12

  of the kidneys · CPC title

• A61K41/00

  Medicinal preparations obtained by treating materials with wave energy or particle radiation {; Therapies using these preparations} · CPC title

• A61K38/13

  Cyclosporins · CPC title