METHODS OF GROWING TUMOR INFILTRATING LYMPHOCYTES IN GAS-PERMEABLE CONTAINERS

• US 20120244133A1
• Filed: 03/20/2012
• Published: 09/27/2012
• Est. Priority Date: 03/22/2011
• Status: Abandoned Application

• Current Assignee: United States Department Of Health And Human Services (Government of the United States of America), Wilson Wolf Manufacturing Corporation
• Original Assignee: Human Services, The United States of America As Represented By The Secretary of Agriculture, Wilson Wolf Manufacturing Corporation
• Inventors: Rosenberg, Steven A., Dudley, Mark E., Wilson, John R., Stroncek, David, Sabatino, Marianna, Jin, Jianjian, Somerville, Robert
• Application Number:
  US13/424,646
• Publication Number:
  US 20120244133A1
• Time in Patent Office: Days
• US Class Current: 424/93.71
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: A61K 2239/57 Skin; melanoma
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4644 Cancer antigens
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C12N 2501/2302 Interleukin-2 (IL-2)
• CPC Class Codes: C12N 2501/2315 Interleukin-15 (IL-15)
• CPC Class Codes: C12N 2501/515 CD3, T-cell receptor complex
• CPC Class Codes: C12N 2502/11 blood or immune system cells
• CPC Class Codes: C12N 5/0634 Cells from the blood or the immune system
• CPC Class Codes: C12N 5/0638 Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]

Abstract

An embodiment of the invention provides a method of promoting regression of cancer in a mammal comprising obtaining a tumor tissue sample from the mammal; culturing the tumor tissue sample in a first gas permeable container containing cell medium therein; obtaining tumor infiltrating lymphocytes (TIL) from the tumor tissue sample; expanding the number of TIL in a second gas permeable container containing cell medium therein using irradiated allogeneic feeder cells and/or irradiated autologous feeder cells; and administering the expanded number of TIL to the mammal. Methods of obtaining an expanded number of TIL from a mammal for adoptive cell immunotherapy are also provided.

Claims

1. A method of obtaining an expanded number of TIL from a mammal for adoptive cell immunotherapy comprising:

obtaining a tumor tissue sample from the mammal;

culturing the tumor tissue sample in a first gas permeable container containing cell medium therein;

obtaining tumor infiltrating lymphocytes (TIL) from the tumor tissue sample;

expanding the number of TIL in a second gas permeable container containing cell medium therein using irradiated allogeneic feeder cells and/or irradiated autologous feeder cells.

6. The method of claim 1, wherein culturing the tumor tissue sample comprises culturing the tumor tissue sample submerged under a height of at least about 1.3 cm of cell culture medium in the first gas permeable container.

7. The method of claim 1, wherein culturing the tumor tissue sample comprises culturing the tumor tissue sample submerged under a height of at least about 2.0 cm of cell culture medium in the first gas permeable container.

8. The method of claim 1, wherein culturing the tumor tissue sample comprises culturing the tumor tissue sample in a gas permeable container having at least about 650 cm² of cell culture surface area.

9. The method of claim 1, wherein the cancer is melanoma.

10. The method of claim 1, wherein expanding the number of TIL comprises culturing the TIL submerged under a height of at least about 1.3 cm of cell culture medium in the second gas permeable container.

11. The method of claim 1, wherein expanding the number of TIL comprises culturing the TIL submerged under a height of at least about 2.0 cm of cell culture medium in the second gas permeable container.

12. The method of claim 1, wherein expanding the number of TIL comprises culturing the TIL in a gas permeable container having at least about 650 cm² of cell culture surface area.

13. The method of claim 1, wherein expanding the number of TIL comprises increasing the number of TIL by at least about 1000-fold.

14. The method of claim 1, comprising expanding the number of TIL in about 5,000 mL to about 10,000 mL of cell medium.

15. The method of claim 1, wherein expanding the number of TIL uses about 1×

10⁹ to about 4×

10⁹ allogeneic feeder cells and/or irradiated autologous feeder cells.

16. The method of claim 1, wherein the cell medium in the first and/or second gas permeable container is unfiltered.

17. The method of claim 1, wherein the cell medium in the first and/or second gas permeable container lacks beta-mercaptoethanol (BME).

18. The method of claim 1, wherein expanding the number of TIL comprises feeding the cells every no more frequently than every third or fourth day.

19. The method of claim 1, wherein the tumor tissue sample is a melanoma tumor tissue sample.

20. The method of claim 1, wherein expanding the number of TIL uses no more than one type of cell culture medium.

21. The method of claim 1, wherein the mammal is a human.

22. The method of claim 1, wherein expanding the number of TIL uses irradiated allogeneic feeder cells and/or irradiated autologous feeder cells at a ratio of about 1 TIL to at least about 20 feeder cells.

23. The method of claim 1, wherein expanding the number of TIL uses irradiated allogeneic feeder cells and/or irradiated autologous feeder cells at a ratio of about 1 TIL to at least about 50 feeder cells.

24. The method of claim 1, wherein expanding the number of TIL uses irradiated allogeneic feeder cells and/or irradiated autologous feeder cells at a ratio of about 1 TIL to at least about 100 feeder cells.

2. A method of promoting regression of cancer in a mammal comprising:

obtaining a tumor tissue sample from the mammal;

culturing the tumor tissue sample in a first gas permeable container containing cell medium therein;

obtaining TIL from the tumor tissue sample;

expanding the number of TIL in a second gas permeable container containing cell medium therein using irradiated allogeneic feeder cells and/or irradiated autologous feeder cells; and

administering the expanded number of TIL to the mammal.

3. A method of obtaining an expanded number of TIL from a mammal for adoptive cell immunotherapy comprising:

obtaining a tumor tissue sample from the mammal;

obtaining TIL from the tumor tissue sample;

expanding the number of TIL in a gas permeable container containing cell medium therein using irradiated allogeneic feeder cells and/or irradiated autologous feeder cells.

5. The method of claim 3, further comprising selecting TIL capable of lysing cancer cells.

4. A method of promoting regression of cancer in a mammal comprising:

obtaining a tumor tissue sample from the mammal;

obtaining TIL from the tumor tissue sample;

expanding the number of TIL in a gas permeable container containing cell medium therein using irradiated allogeneic feeder cells and/or irradiated autologous feeder cells; and

administering the expanded number of TIL to the mammal.