Combined organ and hematopoietic cells for transplantation tolerance of HLA mismatched grafts

Patent metadata

Field	Value
Publication number	US-11648264-B2
Application number	US-201916723840-A
Country	US
Kind code	B2
Filing date	Dec 20, 2019
Priority date	Feb 26, 2013
Publication date	May 16, 2023
Grant date	May 16, 2023

Abstract

Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to an HLA mismatched 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 comprising:
a cryopreservation solution;
an effective amount of CD34+ cells/kilogram recipient weight in the cryopreservation solution;
an effective amount of at least 1×10 7 CD3+ T cells/kilogram recipient weight in the cryopreservation solution; and
a cell type in the cryopreservation solution that facilitates engraftment of cells of the cellular product in a bone marrow of a recipient of a solid organ transplant.

2. The cellular product of claim 1 , wherein the CD34+ cells and the CD3+ cells are derived from a donor that is of an HLA type that is mismatched to the solid organ transplant recipient's HLA type.

3. The cellular product of claim 1 , wherein the effective amount of CD34+ cells/kilogram recipient weight comprises at least 1×10 7 purified CD34+ cells/kilogram recipient weight.

4. The cellular product of claim 1 , wherein the effective amount of CD3+ T cells/kilogram recipient weight comprises at least 4×10 7 CD3+ T cells/kilogram recipient weight.

5. The cellular product of claim 1 , wherein the effective amount of CD3+ T cells/kilogram recipient weight comprises about 5×10 7 CD3+ T cells/kilogram recipient weight.

6. The cellular product of claim 1 , wherein a donor of the solid organ and the donor of the CD34+ cells and the CD3+ cell are the same.

7. The cellular product of claim 1 , wherein the donor of the CD34+ cells and the CD3+ cells is a human.

8. The cellular product of claim 1 , wherein the CD34+ cells and the CD3+ cells are obtained from a deceased or living donor.

9. The cellular product of claim 1 , wherein the cryopreservation solution comprising dimethyl sulfoxide (DMSO).

10. The cellular product of claim 1 , wherein the cryopreservation solution further comprises an isotonic excipient.

11. The cellular product of claim 2 , 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.

12. The cellular product of claim 2 , wherein the CD34+ cells and the CD3+ cells are HLA mismatched to the solid organ transplant recipient at all six HLA alleles.

13. The cellular product of claim 1 , 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

• 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

• A61K2239/38

  characterised by the dose, timing or administration schedule · CPC title