Novel immunotherapy against several tumors including gastrointestinal and gastric cancer

• US 20110229504A1
• Filed: 03/18/2011
• Published: 09/22/2011
• Est. Priority Date: 03/19/2010
• Status: Active Grant

• Current Assignee: Immatics Biotechnologies GmbH (Immatics NV)
• Original Assignee: Immatics Biotechnologies GmbH (Immatics NV)
• Inventors: WEINSCHENK, Toni, WALTER, Steffen, FRITSCHE, Jens, LEWANDROWSKI, Peter, SINGH, Harpreet
• Granted Patent: US 9,101,585 B2
• Time in Patent Office: Days
• US Class Current: 424/185.1
• CPC Class Codes: A61K 2039/5158 Antigen-pulsed cells, e.g. T-cells
• CPC Class Codes: A61K 2039/572 cytotoxic response
• CPC Class Codes: A61K 2039/585 wherein the target is cancer
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/39 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
• CPC Class Codes: A61K 38/4886 Metalloendopeptidases (3.4.24), e.g. collagenase
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids
• CPC Class Codes: C12N 5/0638 Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]
• CPC Class Codes: G01N 33/505 involving T-cells

Abstract

The present invention relates to peptides, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated cytotoxic T cell (CTL) peptide epitopes, alone or in combination with other tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses. The present invention relates to 95 novel peptide sequences and their variants derived from HLA class I molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses.

Claims

1. A peptide comprising a sequence having at least 80% homology to a sequence that is selected from the group consisting of SEQ ID NO:

1 to SEQ ID NO;

95 or a variant thereof, wherein the peptide is capable of inducing T cells cross-reacting with said peptide, and wherein said peptide is not a full-length polypeptide.

2. The peptide according to claim 1, wherein said peptide has an overall length of not more than 100 amino acids.

3. The peptide according to claim 1 having the ability to bind to a molecule of the human major histocompatibility complex (MHC) class-I or -II.

4. The peptide according to claim 1 wherein the peptide consists essentially of an amino acid sequence according to SEQ ID NO:

1 to SEQ ID NO;

95.

5. The peptide according to claim 1, wherein the peptide is modified and/or includes non-peptide bonds.

6. The peptide according to claim 1, wherein the peptide is a fusion protein comprising N-terminal amino acids of the HLA-DR antigen-associated invariant chain (Ii).

7. A nucleic acid, encoding a peptide according to claim 1, provided that the peptide is not the full human protein.

8. The nucleic acid according to claim 7 which is DNA, cDNA, PNA, CNA, RNA or combinations thereof.

9. An expression vector capable of expressing a nucleic acid according to claim 7.

10. A peptide according to claim 1 for use in medicine.

11. A host cell comprising a nucleic acid according to claim 7.

12. The host cell according to claim 11 that is an antigen presenting cell.

13. The host cell according to claim 12, wherein the antigen presenting cell is a dentritic cell.

14. A method of producing a peptide according to claim 1, the method comprising culturing a host cell comprising a nucleic acid encoding the peptide and isolating the peptide from the host cell or its culture medium.

15. An in vitro method for producing activated cytotoxic T lymphocytes (CTL), the method comprising contacting in vitro CTL with antigen loaded human class I or II MHC molecules expressed on the surface of a suitable antigen-presenting cell for a period of time sufficient to activate said CTL in an antigen specific manner, wherein said antigen is a peptide according to claim 1.

16. The method according to claim 15, wherein the antigen is loaded onto class I or II MHC molecules expressed on the surface of a suitable antigen-presenting cell by contacting a sufficient amount of the antigen with an antigen-presenting cell.

17. The method according to claim 15, wherein the antigen-presenting cell comprises an expression vector capable of expressing said peptide.

18. Activated cytotoxic T lymphocytes (CTL), produced by the method according to claim 15, which selectively recognise a cell which aberrantly expresses a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:

1 to SEQ ID NO;

95.

19. A method of killing target cells in a patient which target cells aberrantly express a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:

1 to SEQ ID NO;

95, the method comprising administering to the patient an effective number of cytotoxic T lymphocytes (CTL) as defined in claim 15.

20. A pharmaceutical composition comprising an entity selected from the group consisting of:

a) a peptide according to claim 1;

b) a nucleic acid encoding the peptide;

c) an expression vector capable of expressing the nucleic acid;

d) a host cell comprising the expression vector;

e) an activated cytotoxic T lymphocyte (CTL) produced by an in vitro method comprising contacting in vitro CTL with antigen loaded human class I or II MHC molecules expressed on the surface of a suitable antigen-presenting cell for a period of time sufficient to activate said CTL in an antigen specific manner, wherein said antigen is the peptide.

21. The pharmaceutical composition according to claim 20, wherein the pharmaceutical composition is a vaccine.

22. The pharmaceutical composition according to claim 20, wherein the pharmaceutical composition is active against cancer.

23. The pharmaceutical composition according to claim 22, wherein said cancer cells are gastric cancer cells, gastrointestinal cancer cells, colorectal cancer cells, pancreatic cancer cells, lung cancer cells or renal cancer cells.

24. The peptide of claim 1 comprising a sequence having at least 90% homology to a sequence selected from the group consisting of SEQ ID NO:

1 to SEQ ID NO;

95 or a variant thereof.

25. The peptide of claim 1 comprising a sequence having at least 95% homology to a sequence selected from the group consisting of SEQ ID NO:

1 to SEQ ID NO;

95 or a variant thereof.

26. The peptide of claim 1 comprising a sequence selected from the group consisting of SEQ ID NO:

1 to SEQ ID NO;

95.

27. The peptide of claim 1 having an overall length of not more than 30 amino acids.

28. The peptide of claim 1 having an overall length of not more than 14 amino acids.