Anti-tumor T cell immunity induced by high dose radiation

Patent metadata

Field	Value
Publication number	US-11077141-B2
Application number	US-201816202769-A
Country	US
Kind code	B2
Filing date	Nov 28, 2018
Priority date	Aug 30, 2012
Publication date	Aug 3, 2021
Grant date	Aug 3, 2021

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 treating a cancer in a subject, the method comprising:
a. activating T cells with a high dose of localized radiation at a tumor site;
b. collecting a population of cells comprising the activated T cells and hematopoietic stem cells; and
c. administering the collected population of cells to the subject, thereby treating the cancer.

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

3. The method of claim 2 , wherein the high dose of localized radiation is delivered in a single dose.

4. The method of claim 2 , wherein the high dose of localized radiation is delivered in fractionated doses over a period of time of not more than one week.

5. The method of claim 1 , wherein (a) is performed over a time period from 2 to 6 weeks.

6. The method of claim 1 , further comprising purifying the activated T cells from regulatory T cells and purge tumor cells in the collected population of cells.

7. The method of claim 1 , wherein the collected population of cells comprises allogeneic cells.

8. The method of claim 1 , wherein the collected population of cells comprises autologous cells.

9. The method of claim 1 , wherein the collected population of cells comprises CD34 + cells.

10. The method of claim 1 , wherein activated T cells comprises CD8 + T cells, wherein the CD8 + T cells are activated by the high dose of localized radiation at the tumor site to recognize the cancer.

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

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

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

14. The method of claim 1 , wherein administering the collected population of cells provides for durable remission of the cancer.

15. The method of claim 1 , wherein administering the collected population of cells prevents growth of metastases at a site other than the tumor.

16. The method of claim 1 , wherein administering the collected population of cells stimulates an immune system of the subject to target cancer cells.

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 1 , wherein the subject has been treated with an effective dose of chemotherapy prior to administering the collected population of cells.

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.

22. The method of claim 1 , wherein the cancer is a liver cancer, a lung cancer, a brain cancer, a pancreas cancer, a melanoma cancer, or a breast cancer.

23. The method of claim 1 , wherein the subject is a mammal.

Assignees

• Univ Leland Stanford Junior

Inventors

• Strober Samuel
• Filatenkov Alexander

Classifications

• A61K40/42

  Cancer antigens · CPC title

• A61K40/11

  T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells · CPC title

• A61K2239/50

  Colon · CPC title

• A61K2239/49

  Breast · CPC title

• A61K2239/31

  characterized by the route of administration · CPC title