Novel peptides and combination of peptides 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 the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules. In particular, the present invention relates to several novel peptide sequences and their variants derived from HLA class I and class II molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses or as targets for the development of pharmaceutically/immunologically active compounds and cells.

1 . A method of treating a patient who has a cancer, comprising administering to said patient a composition comprising a population of activated T cells that recognize the cancer cells in the patient that present a peptide consisting of the amino acid sequence of SEQ ID NO: 89, wherein the peptide is in a complex with an MHC molecule, wherein the cancer is liver cancer or small cell lung cancer. 
     
     
         2 . The method of  claim 1 , wherein the T cells are autologous to the patient. 
     
     
         3 . The method of  claim 1 , wherein the T cells are obtained from a healthy donor. 
     
     
         4 . The method of  claim 1 , wherein the T cells are derived from tumor infiltrating lymphocytes or peripheral blood mononuclear cells. 
     
     
         5 . The method of  claim 1 , further comprising expanding T cells in vitro. 
     
     
         6 . The method of  claim 1 , wherein the MHC molecule is a class I MHC molecule. 
     
     
         7 . The method of  claim 1 , wherein the composition further comprises an adjuvant. 
     
     
         8 . The method of  claim 7 , wherein the adjuvant is selected from the group consisting of imiquimod, resiquimod, GM-CSF, cyclophosphamide, Sunitinib, bevacizumab, interferon-alpha, CpG oligonucleotides and derivatives, poly-(I:C) and derivatives, RNA, sildenafil, particulate formulations with poly(lactide co-glycolide) (PLG), virosomes, interleukin (IL)-1, IL-2, IL-4, IL-7, IL-12, IL-13, IL-15, IL-21, and IL-23. 
     
     
         9 . The method of  claim 1 , wherein the activated T cells are cytotoxic T cells produced by contacting T cells with an antigen presenting cell that expresses the peptide in a complex with an MHC class I molecule on the surface of the antigen presenting cell, for a period of time sufficient to activate said T cell specifically against the peptide. 
     
     
         10 . The method of  claim 9 , wherein the T cells contact with an antigen presenting cell in vitro. 
     
     
         11 . The method of  claim 9 , wherein the antigen presenting cell is infected with a recombinant virus expressing the peptide. 
     
     
         12 . The method of  claim 11 , wherein the antigen presenting cell is a dendritic cell or a macrophage. 
     
     
         13 . The method of  claim 9 , further comprising stimulating the activated T cells in the presence of an anti-CD28 antibody and IL-12 to clonally expand the T cells. 
     
     
         14 . The method of  claim 1 , wherein the population of activated T cells comprises CD8-positive cells. 
     
     
         15 . The method of  claim 1 , wherein the cancer is liver cancer. 
     
     
         16 . The method of  claim 1 , wherein the cancer is small cell lung cancer. 
     
     
         17 . A method of treating a patient who has a cancer, comprising administering to said patient a composition comprising a peptide consisting of the amino acid sequence of SEQ ID NO: 89, thereby inducing a T cell response, wherein the cancer is liver cancer or small cell lung cancer. 
     
     
         18 . The method of  claim 17 , wherein the T cell response is a cytotoxic T cell response. 
     
     
         19 . The method of  claim 17 , wherein the cancer is liver cancer. 
     
     
         20 . The method of  claim 17 , wherein the cancer is small cell lung cancer.