Anti-tumor T cell immunity induced by high dose radiation

Patent metadata

Field	Value
Publication number	US-9545444-B2
Application number	US-201514750769-A
Country	US
Kind code	B2
Filing date	Jun 25, 2015
Priority date	Aug 30, 2012
Publication date	Jan 17, 2017
Grant date	Jan 17, 2017

Abstract

Cancer treatment is provided, by irradiating an individual with a localized, high single dose or short course of doses at a primary tumor site; collecting T cells from the individual after a period of time sufficient activation of an anti-tumor response; treating the individual with an effective dose of dose of chemotherapy; and reintroducing the T cell population back to the individual.

First claim

What is claimed is:

1. A method for generating a population of T cells for treating cancer, the method comprising:
subjecting an individual to a high dose of radiation at a tumor site;
collecting a population of cells from the individual after a period of time sufficient for activation of T cells, wherein the collected population of cells comprises T cells and CD34 + cells; and
purifying the T cells from the collected population of cells.

2. The method of claim 1 , further comprising administering the purified T cells to a recipient individual having cancer.

3. The method of claim 1 , wherein the high dose of radiation comprises a total dose of 20 Gy to 40 Gy.

4. The method of claim 1 , wherein the high dose of radiation is delivered in a fractionated dose over a period of time of not more than one week.

5. The method of claim 2 , wherein the cancer is a liver cancer, a lung cancer, a brain cancer, a pancreas cancer, a melanoma cancer, or a breast cancer, and further wherein the cancer is amenable to focused high dose radiation.

6. The method of claim 2 , wherein the administered purified T cells provides for durable remission of the cancer.

7. The method of claim 2 , wherein the administering of the purified T cells prevents growth of metastases at a site other than the tumor site.

8. The method of claim 2 , wherein the administering of the purified T cells stimulates an immune system of the individual to target cancer cells.

9. The method of claim 1 , wherein the collected population of cells comprises CD8 + T cells, wherein the CD8 + T cells are activated by the high dose of radiation to recognize the cancer.

10. The method of claim 1 , wherein the collected population of cells comprises at least 1×10 6 CD8 + T cells.

11. The method of claim 9 , further comprising enriching the CD8 + T cells from the collected population of cells.

12. The method of claim 9 , further comprising purifying the CD8 + T cells from the collected population of cells.

13. The method of claim 2 , wherein the purified T cells comprises allogeneic cells.

14. The method of claim 2 , wherein the purified T cells comprises autologous cells.

15. The method of claim 1 , wherein the collected population of cells is purified from regulatory T cells and purge tumor cells.

16. The method of claim 1 , wherein the period of time sufficient for activation of T cells is from 2 to 6 weeks.

17. The method of claim 1 , wherein the cancer is in an advanced state.

18. The method of claim 1 , wherein the cancer is metastatic.

19. The method of claim 2 , wherein the individual has been treated with an effective dose of chemotherapy.

20. The method of claim 19 , wherein the effective dose of chemotherapy is a non-myeloablative dose.

21. The method of claim 19 , wherein the effective dose of chemotherapy is a myeloablative dose.

Assignees

• Univ Leland Stanford Junior

Inventors

• Strober Samuel
• Filatenkov Alexander

Classifications

• A61K41/0023 Primary

  Aggression treatment or altering · CPC title

• A61N5/10

  X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy (A61N5/01 takes precedence) · CPC title

• A61K45/06 Primary

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K35/28

  Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells · CPC title

• A61P35/00

  Antineoplastic agents · CPC title