METHODS AND COMPOSITIONS CONTAINING mTOR INHIBITORS FOR ENHANCING IMMUNE RESPONSES

• US 20100196311A1
• Filed: 01/14/2010
• Published: 08/05/2010
• Est. Priority Date: 01/14/2009
• Status: Abandoned Application

• Current Assignee: Health Research Incorporated
• Original Assignee: Health Research Incorporated
• Inventors: Rao, Rajesh, Li, Qingsheng, Wang, YanPing, Shrikant, Protul, Kim, Hyung L.
• Application Number:
  US12/687,650
• Publication Number:
  US 20100196311A1
• Time in Patent Office: Days
• US Class Current: 424/85.2
• CPC Class Codes: A61K 2039/55511 Organic adjuvants
• CPC Class Codes: A61K 2039/55516 Proteins; Peptides
• CPC Class Codes: A61K 2039/55538 IL-12
• CPC Class Codes: A61K 2039/6043 Heat shock proteins
• CPC Class Codes: A61K 2239/57 Skin; melanoma
• CPC Class Codes: A61K 2239/59 Reproductive system, e.g. uterus, ovaries, cervix or testes
• 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 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 35/26 Lymph; Lymph nodes; Thymus; Spleen; Splenocytes; Thymocytes
• CPC Class Codes: A61K 38/208 IL-12
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• 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: A61P 37/04 Immunostimulants

Abstract

Provided are compositions and methods for enhancing immune responses to an antigen. The compositions contain an isolated population of CD8+T cells and an inhibitor of mammalian target of rapamycin (mTOR). The method for obtaining an enhanced immune response to an antigen in an individual entails administering to the individual the antigen and an inhibitor of mammalian target of rapamycin (mTOR). CD8+T cells may also be used for adoptive cell transfer (ACT) therapy.

Claims

1. A composition comprising an isolated population of CD8+T cells and an inhibitor of mammalian target of rapamycin (mTOR).

2. The composition of claim 1, wherein the CD8+T cells comprise at least 10% of the cells in the composition.

3. The composition of claim 1, further comprising an antigen to which the CD8+T cells are specific and to which an enhanced immune response in an individual is desired.

4. The composition of claim 3, further comprising interleukin-12 (IL-12).

5. The composition of claim 3, wherein the antigen is a tumor antigen.

6. A method for obtaining an enhanced immune response to an antigen in an individual in need of the enhanced immune response comprising administering to the individual the antigen and an inhibitor of mammalian target of rapamycin (mTOR).

7. The method of claim 6 wherein the individual has been diagnosed with or is suspected of having a cancer, wherein the cancer comprises cancer cells that express the antigen.

8. The method of claim 6, wherein the inhibitor of mTOR is administered to the individual subsequent to the administration of the antigen.

9. The method of claim 8, wherein the inhibitor of mTOR is administered to the individual at least once a day for at least 7 days.

10. The method of claim 8, wherein the inhibitor of mTOR is administered to the individual for not more than 20 consecutive days.

12. The method of claim 6, further comprising administering to the individual a composition comprising isolated CD8+T cells specific for the antigen.

13. The method of claim 12, wherein the antigen has been presented to the CD8+T cells prior to the administering the CD8+T cells to the individual.

14. The method of claim 13, wherein the CD8+T cells have been contacted with an inhibitor of mTOR prior to the administering the CD8+T cells to the individual.

15. The method of claim 12, wherein the CD8+T cells are isolated from the individual prior to the administering the composition comprising the CD8+T cells to the individual.

11. The method of 6, wherein the inhibitor of mTOR is rapamycin or temsirolimus.