Adoptive cell therapy with young T cells

• US 9,074,185 B2
• Filed: 01/16/2013
• Issued: 07/07/2015
• Est. Priority Date: 08/28/2009
• Status: Active Grant

• Current Assignee: United States Department Of Health And Human Services
• Original Assignee: United States Department Of Health And Human Services
• Inventors: Dudley, Mark E., Rosenberg, Steven A.
• Primary Examiner(s): BELYAVSKYI, MICHAIL A
• Application Number:
  US13/742,541
• Publication Number:
  US 20140030806A1
• Time in Patent Office: 902 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/515 Animal cells
• CPC Class Codes: A61K 2239/31 characterized by the route of administration
• CPC Class Codes: A61K 2239/38 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2239/57 Skin; melanoma
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61K 31/7076 containing purines, e.g. adenosine, adenylic acid
• CPC Class Codes: A61K 35/17 Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes when activated by a specific antigen A61K39/00
• CPC Class Codes: A61K 35/26 Lymph; Lymph nodes; Thymus; Spleen; Splenocytes; Thymocytes
• CPC Class Codes: A61K 38/2013 IL-2
• CPC Class Codes: A61K 38/2046 IL-7
• CPC Class Codes: A61K 38/208 IL-12
• CPC Class Codes: A61K 38/2086 IL-13 to IL-16
• 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 2501/23 Interleukins [IL]
• CPC Class Codes: C12N 2501/515 CD3, T-cell receptor complex
• CPC Class Codes: C12N 5/0636 T lymphocytes

Abstract

The invention provides a method of promoting regression of a cancer in a mammal comprising (i) culturing autologous T cells; (ii) expanding the cultured T cells; (iii) administering to the mammal nonmyeloablative lymphodepleting chemotherapy; and (iv) after administering nonmyeloablative lymphodepleting chemotherapy, administering to the mammal the expanded T cells, wherein the T cells administered to the mammal are about 19 to about 35 days old and have not been screened for specific tumor reactivity, whereupon the regression of the cancer in the mammal is promoted.

Claims

1. A method of generating a T cell infusion product for promoting regression of a cancer in a mammal, the method comprising:

(i) culturing autologous T cells;

(ii) enriching the cultured T cells for CD8+ T cells;

(iii) expanding the number of cultured T cells using OKT3 antibody, IL-2, and feeder lymphocytes to provide an expanded number of T cells that are about 19 to about 35 days old; and

(iv) providing the expanded number of T cells that are about 19 to about 35 days old as a cell infusion product,

wherein (ii) is performed prior to (iii), the T cells have not been screened for specific tumor reactivity, and the T cells recognize an antigen of a cancer.

2. The method according to claim 1, comprising producing T cells having a higher expression of CD27 as compared to T cells that are about 44 days old.

3. The method of claim 1, comprising modifying the T-cells to express a T-cell growth factor that promotes the growth and activation of the autologous T-cells.

4. The method of claim 1, comprising modifying the T cells to express a T cell receptor having antigenic specificity for a cancer antigen.

5. The method according to claim 1, comprising producing T cells having a higher expression of CD28 as compared to T cells that are about 44 days old.

6. The method according to claim 1, comprising producing T cells having a mean telomere length that is longer than that of T cells that are about 44 days old.

7. The method according to claim 1, comprising producing T cells having a higher frequency of CD4+ cells as compared to T cells that are about 44 days old.

8. The method according to claim 1, comprising providing an expanded number of T cells that are about 19 to about 26 days old.

9. The method according to claim 1, comprising providing an expanded number of T cells that are about 19 to about 29 days old.

10. The method according to claim 1, comprising providing an expanded number of T cells that are about 23 to about 29 days old.

11. The method according to claim 1, wherein the T cells are capable of promoting regression of a cancer in a mammal.