Combined organ and hematopoietic cells for transplantation tolerance of grafts

Patent metadata

Field	Value
Publication number	US-11040067-B2
Application number	US-201815968396-A
Country	US
Kind code	B2
Filing date	May 1, 2018
Priority date	Feb 26, 2013
Publication date	Jun 22, 2021
Grant date	Jun 22, 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 for establishing mixed chimerism in a solid organ transplant recipient, the method comprising:
providing irradiation and administration of an anti-CD antibody that impacts T-cell activation via CD3 activity to thereby diminishes immune response of the transplant recipient's immune system to the transplanted solid organ, wherein the anti-CD antibody is administered perioperatively to transplantation of a solid organ into the recipient; and
infusing a donor-derived hematopoietic cell composition into the solid organ transplant recipient, the composition comprising at least 10 6 CD34+ cells/kg and at least 10 7 CD3+ cells/kg, to thereby establish mixed chimerism in the solid organ transplant recipient.

2. The method of claim 1 , wherein the mixed chimerism promotes safe withdrawal of immunosuppressive drugs within at least one year of the administering step.

3. The method of claim 1 , wherein the mixed chimerism promotes safe withdrawal of immunosuppressive drugs within at least two years of the administering step.

4. The method of claim 1 , wherein the solid organ transplant recipient is HLA matched to a solid organ transplant donor.

5. The method of claim 1 , wherein the solid organ transplant recipient is HLA mis-matched to a solid organ transplant donor.

6. The method of claim 1 , wherein the transplanted solid organ is a kidney.

7. The method of claim 1 , wherein the anti-CD antibody is a monoclonal antibody.

8. The method of claim 1 , wherein the hematopoietic cell composition comprises
CD34+ cells isolated from an apheresis product from the donor and CD3+ cells isolated from a CD34-depleted fraction of the apheresis product.

9. The method of claim 8 , wherein the CD34-depleted fraction of the apheresis product is a CD34-depleted flow-through fraction from an affinity column.

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