Novel peptides and combination of peptides for use in immunotherapy against ovarian cancer 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.

1 . A method of treating a patient who has cancer, comprising administering to said patient a composition comprising a population of activated T cells that selectively recognize cells in the patient that aberrantly express a peptide, wherein said peptide consists of the amino acid sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 549, wherein said cancer is selected from the group consisting of ovarian cancer, non-small cell lung cancer, small cell lung cancer, kidney cancer, brain cancer, colon or rectum cancer, stomach cancer, liver cancer, pancreatic cancer, prostate cancer, leukemia, breast cancer, Merkel cell carcinoma, melanoma, esophageal cancer, urinary bladder cancer, uterine cancer, gallbladder cancer, and bile duct 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 peptide is in a complex with an 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, resiguimod, GM-CSF, cyclophosphamide, Sunitinib, bevacizumab, interferon-alpha, CpG, oligonucleotides and derivatives, poly-(I:C) and derivatives, RNA, sildenafil, and particulate formations with PLG and virosomes. 
     
     
         9 . The method of  claim 1 , wherein the activated T cells are cytotoxic T cells produced by contacting T cells, in vitro, 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 antigen presenting cell is infected with a recombinant virus expressing the peptide. 
     
     
         11 . The method of  claim 10 , wherein the antigen presenting cell is a dendritic cell or a macrophage. 
     
     
         12 . 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. 
     
     
         13 . The method of  claim 1 , wherein the population of activated T cells comprises CD8-positive cells. 
     
     
         14 . A soluble T-cell receptor (sTCR) that is reactive with an HLA ligand, wherein said ligand consists of the amino acid sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 549. 
     
     
         15 . The sTCR of  claim 14 , wherein the ligand is complexed with a MHC molecule. 
     
     
         16 . The sTCR of  claim 15 , wherein the sTCR binds to the ligand/MHC complex with a binding affinity (KD) of less than about 100 μM. 
     
     
         17 . The sTCR of  claim 15 , wherein the sTCR binds to the ligand/MHC complex with a binding affinity (KD) of less than about 25 nM. 
     
     
         18 . The sTCR of  claim 14 , wherein the sTCR is a heterodimeric molecule comprising a TCR alpha polypeptide chain having a T cell receptor alpha constant domain (TRAC) and a TCR beta polypeptide chain having a T cell receptor beta constant domain 1 (TRBC1) or a T cell receptor beta constant domain 2 (TRBC2). 
     
     
         19 . An antibody that specifically binds to a peptide consisting of the amino acid sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 83 and SEQ ID NO: 85 to SEQ ID NO: 549 or binds to the peptide consisting of the amino acid sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 83 and SEQ ID NO: 85 to SEQ ID NO: 549 bound to an MHC molecule. 
     
     
         20 . The antibody of  claim 19 , wherein said antibody is a polyclonal antibody, a monoclonal antibody, a bi-specific antibody, or a chimeric antibody.