Enhancement of allogeneic hematopoietic stem cell transplantation

Patent metadata

Field	Value
Publication number	US-9833477-B2
Application number	US-201615217363-A
Country	US
Kind code	B2
Filing date	Jul 22, 2016
Priority date	Jan 10, 2011
Publication date	Dec 5, 2017
Grant date	Dec 5, 2017

Abstract

Methods and compositions are provided to augment the conversion of mixed hematopoietic cell chimerism to complete donor cell chimerism following allogeneic hematopoietic cell transplantation (HCT), where such transplantation may be utilized for treatment of cancer such as leukemia and lymphoma or for other conditions requiring reconstitution of the hematopoietic system, e.g. treatment of anemias, thalassemias, autoimmune conditions, and the like. The present invention improves on conventional DLI by utilizing a composition of substantially purified donor memory CD8 + T cells as DLI following allogeneic HCT, where the cells are administered at a suitable time following transplantation. The methods provide for a more complete donor chimerism, and have the further benefit of killing tumor cells without GVHD. The memory CD8+ T cells may include one or both of central and effector memory T cells, usually both.

First claim

What is claimed is:

1. A method of treating a cancer or reducing a likelihood of cancer relapse in a human subject by reconstituting said human subject hematopoietic system, said method comprising:
administering to said human subject a dose of donor-derived T cells following an allogeneic hematopoietic cell transplantation, wherein said donor-derived T cells comprise memory CD8+ T cells, wherein said memory CD8+ T cells comprise CD8+CD45RA − memory CD8+ T cells or CD8+CD45RO + memory CD8+ T cells, wherein said dose is administered at least two months following said allogenic hematopoietic cell transplantation, and wherein said dose is effective to promote complete chimerism.

2. The method of claim 1 , wherein said cancer is lymphoma.

3. The method of claim 1 , wherein said cancer is leukemia.

4. The method of claim 1 , wherein said cancer is a hematologic malignancy.

5. The method of claim 1 , wherein said cancer is a solid tumor.

6. The method of claim 1 , wherein said administering treats or reduces the likelihood of cancer relapse.

7. The method of claim 1 , wherein said administering kills residual cancer cells in said human subject.

8. The method of claim 1 , wherein said human subject is at least in partial remission from said cancer.

9. The method of claim 1 , wherein said dose comprises at least 1×10 6 donor-derived T cells.

10. The method of claim 1 , wherein said dose comprises at least 1×10 8 donor-derived T cells.

11. The method of claim 9 , wherein said memory CD8+ T cells comprises central and effector memory T cells.

12. The method of claim 1 , wherein said memory CD8+ T cells are at least 80% pure.

13. The method of claim 9 , wherein said memory CD8 + T cells are human cells.

14. The method of claim 13 , wherein said memory CD8 + T cells are obtained and are used directly, frozen or maintained ex vivo in an appropriate culture medium.

15. The method of claim 1 , wherein said human subject is an individual human selected from a pediatric patient and an adult patient.

16. The method of claim 1 , wherein said administering further provides for an absence of graft versus host disease.

17. The method of claim 1 , wherein said human subject has been treated with a chemotherapeutic agent or a radiological agent.

Assignees

• Univ Leland Stanford Junior

Inventors

• Strober Samuel
• Dutt Suparna
• Lowsky Robert

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61K2035/124

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

• A61P37/02

  Immunomodulators · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P7/06

  Antianaemics · CPC title