Attack of tumor cells with missing, low or aberrant MHC expression by combining non MHC-restricted T-cells/NK-cells and MHC-restricted cells

• US 20030095955A1
• Filed: 07/05/2002
• Published: 05/22/2003
• Est. Priority Date: 07/05/2001
• Status: Active Grant

• Current Assignee: Helmholtz Zentrum Munchen Forschungszentrum Fur Gesundheit und Umwelt GmbH
• Original Assignee: Helmholtz Zentrum Munchen Forschungszentrum Fur Gesundheit und Umwelt GmbH
• Inventors: Weiss, Elisabeth, Falk, Christine, Schendel, Dolores, Noessner, Elfriede
• Granted Patent: US 7,731,950 B2
• Time in Patent Office: Days
• US Class Current: 424/93.21
• 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 39/4613 Natural-killer cells [NK or NK-T]
• CPC Class Codes: A61K 39/4644 Cancer antigens
• CPC Class Codes: A61K 39/464838 Viral antigens
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

This invention is directed to therapeutic compositions containing non-MHC-restricted T-cells/NK-cells cells/NK-cells in combination with MHC-restricted T-cells and especially to therapeutic compositions, which comprise LAK cells. Furthermore, the present invention is directed to the use of the above combination in the treatment of tumors in humans, which tumors show a missing, low or aberrant expression of MHC class 1a or 1b molecules. By using the aforementioned compositions/combinations it is possible to provide a balanced selective pressure against emergence of tumor cell variants that would otherwise escape immune detection.

Claims

1. A therapeutic composition containing

a) non-MHC-restricted T-cells and/or Natural Killer (NK) cells in combination with

b) MHC-restricted T-cells or

c) therapeutic agents, which induce immune responses of MHC-restricted T cells.

2. The therapeutic composition of claim 1, wherein the cells in a) consist of Lymphokine Activated Killer (LAK) cells.

3. The therapeutic composition of claim 1, wherein the cells in a) consist of LAK-T-cells.

4. The therapeutic composition of any of claims 1, wherein the therapeutic agent for inducing MHC-restricted T-cell responses is a genetically engineered tumor cell.

5. The therapeutic composition of any of claims 1, wherein the therapeutic agent for inducing MHC-restricted T-cell responses is a vaccine comprising tumor cells or dendritic cells.

6. A pharmaceutical composition comprising the composition of claim 1 and a pharmaceutically acceptable carrier.

7. A method of therapeutically treating a patient suffering from a tumor disease, said method comprising administering to said patient a therapeutically effective dosage of a composition of claim 6.

8. The method of claim 7, wherein tumors are treated, which show a low, missing or aberrant expression of MHC class Ia or Ib molecules.

9. The method of claim 8, wherein the tumors show a low, missing or aberrant expression of HLA-C and/or HLA-E molecules.

10. A method of therapeutically treating a patient suffering from a tumor disease, said method comprising administering to said patient a therapeutically effective dosage of

a) activated non-MHC-restricted T-cells and/or Natural Killer (NK) cells and

b) MHC-restricted T-cells or

c) therapeutic agents, which induce responses of MHC-restricted T cells, in a method for the treatment of tumors, which show a low, missing or aberrant expression of MHC class Ia or Ib molecules.

11. The method of claim 10, wherein the tumors show a low, missing or aberrant expression of HLA-C and/or HLA-E molecules.

12. The method of claim 10, which comprises the step of applying non MHC-restricted T-cells and/or NK cells prior to applying MHC-restricted T-cells or therapeutic agents for inducing MHC-restricted T cell responses.

13. The method of claim 10, which comprises the step of applying non MHC-restricted T-cells and/or NK cells simultaneously with applying MHC-restricted T-cells or therapeutic agents for inducing MHC-restricted T cell responses.

14. The method of claim 10, which comprises the step of applying non MHC-restricted T-cells and/or NK cells subsequent to applying MHC-restricted T-cells or therapeutic agents for inducing MHC-restricted T cell responses.

15. The method of claim 10, which further comprises the step of initially determining the MHC class I expression in the tumor.

16. The method of claim 10, wherein the non MHC-restricted T-cells and/or NK cells consist of LAK cells.

17. The method of claim of 7 or 10, wherein a mammal is treated.

18. The method of claim 7 or 10, wherein a human being is treated.

19. The method of claims 7 or 10, wherein the tumor is selected from colon carcinoma, breast carcinoma, prostate carcinoma, renal cell carcinoma (RCC) or melanoma.

20. A kit of parts, containing

a) non-MHC-restricted T-cells and/or Natural Killer (NK) cells in combination with

b) MHC-restricted T-cells or

c) therapeutic agents, which induce immune responses of MHC-restricted T cells.

21. The kit of parts of claim 20, wherein the cells in a) consist of Lymphokine Activated Killer (LAK) cells.

22. The kit of parts of claim 20, wherein the cells in a) consist of LAK-T-cells.

23. The kit of parts of claim 20, wherein the therapeutic agent for inducing MHC-restricted T-cell responses is a genetically engineered tumor cell.

24. The kit of parts of claim 20, wherein the therapeutic agent for inducing MHC-restricted T-cell responses is a vaccine comprising tumor cells or dendritic cells.