NOVEL IMMUNOTHERAPY AGAINST SEVERAL TUMORS, SUCH AS LUNG CANCER, INCLUDING NSCLC

• US 20170202937A1
• Filed: 11/21/2016
• Published: 07/20/2017
• Est. Priority Date: 08/05/2013
• Status: Active Grant

• Current Assignee: Immatics Biotechnologies GmbH (Immatics NV)
• Original Assignee: Immatics Biotechnologies GmbH (Immatics NV)
• Inventors: FRITSCHE, Jens, WALTER, Steffen, Song, Colette, SINGH, Harpreet, WEINSCHENK, Toni
• Granted Patent: US 10,071,148 B2
• Time in Patent Office: Days
• 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 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 38/1709 from mammals
• CPC Class Codes: A61K 39/0011 Cancer 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 37/04 Immunostimulants
• CPC Class Codes: C07K 14/7051 T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68
• CPC Class Codes: C12N 2502/11 blood or immune system cells
• CPC Class Codes: C12N 5/0636 T lymphocytes
• CPC Class Codes: C12N 5/0638 Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]
• CPC Class Codes: C12N 9/6491 Matrix metalloproteases [MMP's], e.g. interstitial collagenase (3.4.24.7); Stromelysins (3.4.24.17; 3.2.1.22); Matrilysin (3.4.24.23)
• CPC Class Codes: C12Y 304/24065 Macrophage elastase (3.4.24.65), i.e. metalloelastase

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 more than 70 novel peptide sequences and their variants derived from HLA class I and HLA class II molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses.

Claims

1. A peptide comprising an amino acid sequence of SEQ ID 2, or a variant sequence thereof which is at least 80% homologous to SEQ ID No. 2, wherein said variant induces antibodies and/or T cells specifically binding to said peptide, or a pharmaceutical acceptable salt of SEQ ID No. 2, wherein said peptide is not the underlying full-length polypeptide.

2. The peptide according to claim 1, wherein said peptide or variant thereof has an overall length of between 8 and 100, optionally between 8 and 30, of optionally between 8 and 14 amino acids for a peptide comprising SEQ ID No. 2.

3. The peptide according 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 claim 1, wherein said peptide consists or consists essentially of an amino acid sequence according to SEQ ID No. 2.

5. The peptide according to claim 1, wherein said peptide is modified, elongated N- and/or C-terminally by up to four amino acids, and/or includes non-peptide bonds.

6. The peptide according to claim 1, wherein said peptide is a part of a fusion protein, optionally fused to the N-terminal amino acids of the HLA-DR antigen-associated invariant chain (Ii), or is fused to an antibody.

7. A nucleic acid, encoding for a peptide according to claim 1.

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

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

10. The peptide according to claim 1 capable for use in medicine.

11. A host cell, comprising the nucleic acid according to claim 7, wherein said host cell is not a human embryonic stem cell.

12. The host cell according to claim 11, wherein said cell is an antigen presenting cell, optionally a dendritic cell.

13. A pharmaceutical composition comprising the peptide according to claim 1 or a pharmaceutical acceptable salt thereof, and at least one other component selected from the group of pharmaceutically acceptable, optionally aqueous, carriers and/or excipients, optionally buffers, binding agents, blasting agents, diluents, flavours, lubricants, and immune stimulating or immune modulating substances, such as cytokines, immuno-modulators, adjuvants and therapeutic substances with immune modulating properties.

14. Method for producing a peptide the method comprising culturing the host cell according to claim 11, and isolating said peptide from the host cell or culture medium thereof.

15. An in vitro method for producing an activated cytotoxic T lymphocyte (CTL) or T helper cell (Th cell), the method comprising contacting in vitro a CTL or Th cell 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 according to claim 1.

16. The method according to claim 15, wherein said 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 said antigen with said antigen-presenting cell.

17. The method according to claim 151, wherein said antigen-presenting cell comprises an expression vector capable of expressing a peptide according to claim 1.

18. An activated cytotoxic T lymphocyte (CTL) or T helper cell (Th cell), produced by the method according to claim 15, wherein said CTL or Th cell selectively recognises a cell which aberrantly expresses a polypeptide comprising an amino acid sequence as given in said peptide.

19. An in vitro method for producing a TCR or sTCR or fragment thereof that is specific for the peptide according to claim 1, comprising cloning of variable domains from an activated cytotoxic T lymphocyte (CTL) or T helper cell (Th cell), and expressing said TCR or sTCR or fragment thereof in a suitable host and/or expression system.

20. An isolated binding agent optionally an antibody or fragment thereof, a protein, a nucleic acid, a peptide, a TCR or an sTCR or fragment thereof that binds, and optionally binds specifically, to the peptide according to claim 1 or to a complex of the peptide.

23. A method of killing target cells in a patient, wherein said target cells aberrantly express and/or present a polypeptide comprising an amino acid sequence as given in claim 1, the method comprising administering to said patient an effective number of cytotoxic T lymphocytes (CTL) or Th cells.

24. A peptide according to claim 1 as a medicament, wherein said medicament is active against cancer.

25. The peptide according to claim 24, wherein said medicament is a vaccine.

26. The peptide according to claim 24, wherein said cancer is selected from non-small cell lung carcinoma (NSCLC), lung cancer, gastric cancer, and/or glioblastoma.

27. The peptide according to claim 24 for adoptive cellular therapy in humans.

28. An autologous or allogeneic human cytotoxic T cell (CTL) or T helper cell (Th cell), recombinantly transfected with an isolated binding agent optionally a T-cell receptor according to claim 20.

29. A pharmaceutical composition comprising:

(a) an entity selected from the group consisting of;

(a1) an isolated peptide according to claim 1,

(a2) a T cell receptor, sTCR or fragment thereof

(a3) a fusion protein

(a4) a nucleic acid

(a5) an expression vector

(a6) a host cell

(a7) an activated cytotoxic T lymphocyte or T helper cell wherein a2-a7 comprise or are derived from said peptide, and

(b) a pharmaceutically acceptable carrier, and optionally

(c) at least one other component selected from the group of pharmaceutically acceptable excipients, buffers, binding agents, blasting agents, diluents, flavours, lubricants, and immune stimulating or immune modulating substances, such as cytokines, immunomodulators, adjuvants and therapeutic substances with immune modulating properties

21. An isolated T-cell receptor reactive with an HLA ligand that is at least 80% identical with an amino acid sequence of SEQ ID 2.

22. The isolated T-cell receptor of claim 21, wherein said amino acid sequence is at least 90%, optionally at least 95%, optionally 100% identical to SEQ ID No. 2.