NEW PEPTIDES AND PEPTIDE COMBINATIONS FOR USE IN IMMUNOTHERAPY AGAINST HEPATOCELLULAR CARCINOMA (HCC) AND OTHER CANCERS

Abstract

The present invention relates to peptides, proteins, nucleic acids, and cells for use in immunotherapeutic methods. In particular, the present invention relates to cancer immunotherapy. The present invention further relates to tumor peptide epitopes of T cells, alone or in combination with other tumor peptides, which can, for example, serve as active pharmaceutical ingredients in vaccine compositions intended to stimulate an antitumor immune response or to stimulate T cells ex vivo for subsequent transfer to the patient. Peptides bound to major histocompatibility complex (MHC) molecules, or the peptides themselves, can also be targets of antibodies, soluble T cell receptors, and other binding molecules.The present invention relates in particular to several novel peptide sequences and their variants derived from human tumor cell class i and class ii hla molecules, which can be used in vaccine compositions to induce an antitumor immune response, or as targets for the development of pharmaceutically / immunologically active compounds and cells.

Description

to induce an antitumor immune response, or as targets for the development of pharmaceutically / immunologically active compounds and cells.

Claims

EP 15 813 809.9 I32728WOEP DEMANDS 1. A peptide comprising the amino acid sequence SEQ ID n° 53, and a pharmaceutically acceptable salt thereof, wherein said peptide has an overall length of between 10 and 30 amino acids, wherein said peptide has the capacity to bind to a molecule of the human major histocompatibility complex (MHC) class I, and wherein said peptide, when bound to the MHC, has the capacity to be recognized by CD8 T lymphocytes 2. Peptide, or variant thereof, according to claim 1, wherein said peptide has an overall length of between 10 and 16 amino acids, and even more preferably wherein the peptide consists of an amino acid sequence conforming to SEQ ID No.

53.

3. Peptide according to claim 1 or 2, wherein said peptide comprises non-peptide linkages and / or said peptide is part of a fusion protein comprising N-terminal amino acids of the invariant chain (li) associated with the antigens of the HIA-DR system.

4. Antibody, soluble or membrane-bound, which specifically recognizes the peptide according to claim 1 or 2, preferably the peptide according to claim 1 or 2 which is bound to an MHC molecule.

5. T cell receptor (TCR), soluble or membrane-bound, which reacts with an HIA ligand, wherein said ligand is at least 88% identical to, and preferably consists of, the amino acid sequence selected from the group consisting of SEQ ID n0 53, wherein optionally said TCR is provided in the form of a soluble molecule and optionally exhibits an additional effector function such as an immunostimulatory domain or a toxin.

6. Nucleic acid, encoding a peptide according to any one of claims 1 to 3, antibody according to claim 4, TCR according to claim 5 or expression vector expressing said nucleic acid.

7. Host cell comprising the peptide according to any one of claims 1 to 3, or the nucleic acid or expression vector according to claim 6, wherein said host cell is preferably an antigen-presenting cell such as a dendritic cell, a T lymphocyte or an NK cell.

8. A method for producing the peptide according to any one of claims 1 to 3, the antibody according to claim 4, or the TCR according to claim 5, said method comprising culturing a host cell according to claim 7 which presents the peptide according to any one of claims 1 to 3, or expresses the nucleic acid or expression vector according to claim 6, and isolating said peptide, said antibody or said TCR from the host cell and / or its culture medium.

9. In vitro process for producing active T lymphocytes, said process comprising in vitro contact of T lymphocytes with human MHC class I molecules loaded with antigens expressed on the surface of a suitable antigen-presenting cell or an artificial construct mimicking an antigen-presenting cell for a time sufficient to activate said T lymphocytes in an antigen-specific manner, wherein said antigen is a peptide according to claim 1 or 2.

10. active T lymphocyte, produced by the process according to claim 9, which selectively recognizes a cell that presents a polypeptide comprising an amino acid sequence as described in claim 1 or 2.

11. Pharmaceutical composition comprising at least one active ingredient selected from the group consisting of the peptide according to any one of claims 1 to 3, the antibody according to claim 4, the TCR according to claim 5, the acid nucleic acid or the expression vector according to claim 6, the host cell comprising the expression vector according to claim 7, the active T lymphocyte according to claim 10, and a pharmaceutically acceptable carrier, and optionally, pharmaceutically acceptable excipients and / or stabilizers.

12. Peptide according to any one of claims 1 to 3, antibody according to claim 4, TCR according to claim 5, nucleic acid or expression vector according to claim 6, host cell comprising the expression vector according to claim 7, activated T lymphocyte according to claim 10, or pharmaceutical composition according to claim 11 for medical use.

13. Peptide according to any one of claims 1 to 3, antibody according to claim 4, TCR according to claim 5, nucleic acid or expression vector according to claim 6, host cell comprising the expression vector according to claim 7, activated T lymphocyte according to claim 10, or pharmaceutical composition according to claim 11 for use in the treatment of cancer.

14. Peptide according to any one of claims 1 to 3, antibody according to claim 4, TCR according to claim 5, nucleic acid or expression vector according to claim 6, host cell comprising the expression vector according to claim 7, activated T lymphocyte according to claim 10, or pharmaceutical composition according to claim 11 for use according to claim 13, wherein said cancer is selected from the group consisting of HCC, brain cancer, renal cancer, pancreatic cancer, colon or rectal cancer or leukemia and other tumors that exhibit CFHR5 overexpression.

15. Kit includes: (a) a container containing a pharmaceutical composition according to claim 11, in the form of a solution or in lyophilized form; (b) optionally, a second container containing a diluent or a reconstitution solution for the lyophilized formulation; (c) Optionally, at least one additional peptide selected from the group consisting of SEQ ID n1 to SEQ ID n52 and SEQ ID n54 to SEQ ID n346, and (d) optionally, instructions on (i) use of the solution or (ii) reconstitution and / or use of the lyophilized formulation, and, optionally, also including one or more of the following components: (iii) buffer, (iv) diluent, (v) filter, (vi) needle or (vii) syringe.