Peptides and combination thereof for use in the immunotherapy against 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 that presents a peptide consisting of the amino acid sequence of SEQ ID NO: 8, 21, 231, 104, 100, 156, 170, 102, or 101 in a complex with an MHC class I molecule on the surface of cancer cells, comprising administering to said patient a population of activated CD8+ cytotoxic T cells that recognize cancer cells that present a peptide consisting of the amino acid sequence of SEQ ID NO: 8, 21, 231, 104, 100, 156, 170, 102, or 101,
 wherein said cancer is selected from the group consisting of colorectal cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, renal cell carcinoma, chronic lymphocytic leukemia, chronic myeloid leukemia and acute myeloid leukemia, non-Hodgkin lymphoma, esophageal cancer, non-small cell lung cancer, small cell lung cancer, pancreatic cancer, prostate cancer, melanoma, breast cancer, gallbladder cancer and cholangiocarcinoma, urinary bladder cancer, uterine cancer, head and neck squamous cell carcinoma, and mesothelioma.   
     
     
         2 . The method of  claim 1 , wherein the CD8+ cytotoxic T cells are autologous to the patient. 
     
     
         3 . The method of  claim 1 , wherein the CD8+ cytotoxic T cells are obtained from a healthy donor. 
     
     
         4 . The method of  claim 1 , wherein the CD8+ cytotoxic T cells are obtained from tumor infiltrating lymphocytes or peripheral blood mononuclear cells. 
     
     
         5 . The method of  claim 1 , wherein the activated CD8+ cytotoxic T cells are expanded in vitro. 
     
     
         6 . The method of  claim 1 , further comprising administering to said patient an adjuvant. 
     
     
         7 . The method of  claim 6 , wherein the adjuvant is selected from imiquimod, resiquimod, GM-CSF, interferon-alpha, interferon-beta, CpG oligonucleotides, poly-(I:C), virosomes, interleukin (IL)-1, IL-2, IL-4, IL-7, IL-12, IL-13, IL-15, IL-21, and IL-23. 
     
     
         8 . The method of  claim 1 , further comprising administering said patient cyclophosphamide, sunitinib, bevacizumab, or sildenafil. 
     
     
         9 . The method of  claim 1 , wherein the activated CD8+ cytotoxic T cells are produced by contacting CD8+ cytotoxic 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 CD8+ cytotoxic T cell. 
     
     
         10 . The method of  claim 9 , wherein the antigen presenting cell is infected with a recombinant virus expressing the peptide. 
     
     
         11 . A method of eliciting an immune response in a patient who has cancer that presents a peptide consisting of the amino acid sequence of SEQ ID NO: 8, 21, 231, 104, 100, 156, 170, 102, or 101 in a complex with an MHC class I molecule on the surface of cancer cells, comprising administering to said patient a population of activated CD8+ cytotoxic T cells that recognize cancer cells that present a peptide consisting of the amino acid sequence of SEQ ID NO: 8, 21, 231, 104, 100, 156, 170, 102, or 101,
 wherein said cancer is selected from the group consisting of colorectal cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, renal cell carcinoma, chronic lymphocytic leukemia, chronic myeloid leukemia and acute myeloid leukemia, non-Hodgkin lymphoma, esophageal cancer, non-small cell lung cancer, small cell lung cancer, pancreatic cancer, prostate cancer, melanoma, breast cancer, gallbladder cancer and cholangiocarcinoma, urinary bladder cancer, uterine cancer, head and neck squamous cell carcinoma, and mesothelioma.   
     
     
         12 . The method of  claim 11 , wherein the CD8+ cytotoxic T cells are autologous to the patient. 
     
     
         13 . The method of  claim 11 , wherein the CD8+ cytotoxic T cells are obtained from a healthy donor. 
     
     
         14 . The method of  claim 11 , wherein the CD8+ cytotoxic T cells are obtained from tumor infiltrating lymphocytes or peripheral blood mononuclear cells. 
     
     
         15 . The method of  claim 11 , wherein the activated CD8+ cytotoxic T cells are expanded in vitro. 
     
     
         16 . The method of  claim 11 , further comprising administering to said patient an adjuvant. 
     
     
         17 . The method of  claim 16 , wherein the adjuvant is selected from imiquimod, resiquimod, GM-CSF, interferon-alpha, interferon-beta, CpG oligonucleotides, poly-(I:C), virosomes, interleukin (IL)-1, IL-2, IL-4, IL-7, IL-12, IL-13, IL-15, IL-21, and IL-23. 
     
     
         18 . The method of  claim 11 , further comprising administering said patient cyclophosphamide, sunitinib, bevacizumab, or sildenafil. 
     
     
         19 . The method of  claim 11 , wherein the activated CD8+ cytotoxic T cells are produced by contacting CD8+ cytotoxic 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 CD8+ cytotoxic T cell. 
     
     
         20 . The method of  claim 19 , wherein the antigen presenting cell is infected with a recombinant virus expressing the peptide.