CANCER THERAPY BASED ON TUMOR ASSOCIATED ANTIGENS DERIVED FROM CYCLIN D1

• US 20120027684A1
• Filed: 06/01/2011
• Published: 02/02/2012
• Est. Priority Date: 06/02/2010
• Status: Active Grant

• Current Assignee: Immatics Biotechnologies GmbH (Immatics NV)
• Original Assignee: Immatics Biotechnologies GmbH (Immatics NV)
• Inventors: SINGH, Harpreet, WEINSCHENK, Toni, WALTER, Steffen
• Granted Patent: US 9,056,069 B2
• Time in Patent Office: Days
• US Class Current: 424/9.2
• 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 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]
• CPC Class Codes: A61K 38/20 Interleukins [IL]
• CPC Class Codes: A61K 38/2013 IL-2
• CPC Class Codes: A61K 38/2026 IL-4
• CPC Class Codes: A61K 38/21 Interferons [IFN]
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/001149 Cell cycle regulated proteins, e.g. cyclin, CDC, CDK or INK-CCR
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• 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 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/4738 Cell cycle regulated proteins, e.g. cyclin, CDC, INK-CCR cell cycle dependent kinases C12N9/12
• CPC Class Codes: C12N 5/0638 Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]
• CPC Class Codes: G01N 2800/24 Immunology or allergic disorders
• CPC Class Codes: G01N 2800/7028 : Cancer

Abstract

The present invention relates to cyclin D1-derived peptides for use in the improved treatment of cancer in a patient, particularly in the form of a combination therapy using a vaccine. Other aspects relate to the use of the peptides or a combination thereof as a diagnostic tool.

Claims

1. At least one peptide consisting essentially of an amino acid sequence selected from the group consisting of SEQ ID NO:

1 to SEQ ID NO;

18.

2. The peptide according to claim 1, wherein said peptide is selected from the group consisting of SEQ ID NO:

1, SEQ ID NO;

4, and SEQ ID NO;

18.

3. A pharmaceutical composition comprising at least one peptide according to claim 1.

4. The pharmaceutical composition according to claim 3, wherein said composition is formulated for treatment of a cancer selected from the group consisting of lung cancer, head and neck cancer, breast cancer, pancreatic cancer, prostate cancer, renal cancer, esophageal cancer, bone cancer, testicular cancer, cervical cancer, gastrointestinal cancer, glioblastoma, leukemia, lymphomas, mantle cell lymphoma, pre-neoplastic lesions in the lung, colon cancer, melanoma, bladder cancer and any other neoplastic diseases.

5. The pharmaceutical composition according to claim 3, wherein said pharmaceutical composition is capable of being administered in the form of an anti-cancer vaccine.

6. The pharmaceutical composition according to claim 3, further comprising at least one adjuvant.

7. The pharmaceutical composition according to claim 6, wherein the adjuvant is GM-CSF.

8. The pharmaceutical composition according to claim 3, further comprising at least one tumor associated peptide which is not derived from cyclin D1.

9. The pharmaceutical composition according to claim 8, wherein the at least one tumor associated peptide is selected from the group consisting of SEQ ID NO:

19 to SEQ ID NO;

26.

10. The pharmaceutical composition according to claim 8, wherein the at least one tumor associated peptide which is not derived from cyclin D1 is chosen based on its ability to bind to a different HLA-molecule, as compared with the at least one peptide selected from the group consisting of SEQ ID NO 1 to SEQ ID NO 18.

11. A method of treating cancer comprising administering to a subject in need thereof a pharmaceutical composition according to claim 3.

12. The method of claim 11, wherein said pharmaceutical composition is administered repeatedly.

13. The method of claim 12, wherein said pharmaceutical composition is administered monthly, weekly, or twice a week.

14. The method of claim 11, further comprising a treatment with at least one chemotherapeutic agent.

15. The method of claim 14, wherein said chemotherapeutic agent is an agent capable of inactivating and/or eliminating a population of immunoregulatory cells in said subject.

16. The method of claim 15 wherein the population of immunoregulatory cells is CD4⁺ CD25⁺ regulatory T cells and the chemotherapeutic agent is cyclophosphamide

17. The method of claim 14, wherein the treatment with the at least one chemotherapeutic agent takes place before administration of said composition.

18. The method of claim 17, wherein the chemotherapeutic agent is given as a single dosage.

19. The method of claim 18, wherein cyclophosphamide is given in a dosage of 300 mg/m² as a single infusion.

20. The method of claim 11, wherein the pharmaceutical composition is administered as an adjuvant treatment following a prior tyrosine kinase inhibitor therapy and/or a prior cytokine therapy.

21. The method of claim 20, wherein the tyrosine kinase inhibitor therapy comprises sunitinib and/or sorafenib and the cytokine therapy comprises an interferon and/or an interleukin.

22. The method of claim 11, comprising a cytokine therapy, followed by a single-dose cyclophosphamide therapy, followed by the administration of the pharmaceutical composition for priming for about daily for about a week, and then administration of the pharmaceutical composition every two weeks for at least 6 months.

23. A method for producing an activated cytotoxic T lymphocytes (CTL) in vitro, comprising contacting the CTL with at least one peptide of claim 1 loaded onto a human class I or II MHC molecule expressed on the surface of an antigen-presenting cell for a period of time sufficient to activate said CTL in an antigen specific manner.

24. A method of detecting and/or monitoring an activation and/or modulation of the immune system of a patient comprising using at least one peptide according to claim 1.

25. The method of claim 24, wherein the activation and/or modulation of the immune system is used as a diagnostic tool in diagnosis of cancer.

27. A combination comprising at least two peptides according to claim 1.

26. A tumor associated peptide consisting of or essentially consisting of an amino acid sequence selected from SEQ ID NO:

5 and/or SEQ ID NO;

6.