Novel peptides and combination of peptides for use in immunotherapy against esophageal 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 peptide consisting of the amino acid sequence selected from the group consisting of SEQ ID NO: 9, 11-13, 26, 32, 67, 80, 82, 1-8, 10, 14-25, 27-31, 33-66, 68-79, 81, and 83-101 in the form of a pharmaceutically acceptable salt. 
     
     
         2 . A modified peptide consisting of the amino acid sequence selected from the group consisting of SEQ ID NO: 9, 11-13, 26, 32, 67, 80, 82, 1-8, 10, 14-25, 27-31, 33-66, 68-79, 81, and 83-101 comprising at least one non-peptide bond or at least one D-amino acid substitution. 
     
     
         3 . The peptide according to  claim 1 , wherein the pharmaceutically acceptable salt is a chloride salt, acetate salt, or trifluoro-acetate salt. 
     
     
         4 . A pharmaceutical composition comprising the peptide according to  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         5 . The pharmaceutical composition according to  claim 4 , wherein the pharmaceutically acceptable carrier is selected from the group consisting of saline, Ringer's solution and dextrose solution. 
     
     
         6 . The pharmaceutical composition according to  claim 4 , further comprising pharmaceutically acceptable excipients and/or stabilizers. 
     
     
         7 . The pharmaceutical composition according to  claim 6 , wherein said pharmaceutically acceptable excipients are selected from the group consisting of buffers, binding agents, diluents, flavors, and lubricants. 
     
     
         8 . The modified peptide of  claim 2 , comprising at least one non-peptide bond. 
     
     
         9 . The modified peptide of  claim 2 , wherein the at least one non-peptide bond is selected from —CH 2 —NH, —CH 2 S—, —CH 2 CH 2 —, —CH═CH—, —COCH 2 —, —CH(OH)CH 2 —, or —CH 2 SO—. 
     
     
         10 . The modified peptide of  claim 2 , comprising at least one D-amino acid substitution. 
     
     
         11 . The peptide of  claim 3 , wherein the pharmaceutically acceptable salt is the trifluro-acetate salt. 
     
     
         12 . The peptide of  claim 3 , wherein the pharmaceutically acceptable salt is the chloride salt. 
     
     
         13 . A pharmaceutical composition comprising the peptide of  claim 1  and an immune-enhancing amount of an adjuvant. 
     
     
         14 . The pharmaceutical composition of  claim 18 , wherein the adjuvant is at least one selected from the group consisting of anti-CD40 antibody, imiquimod, resiquimod, GM-CSF, cyclophosphamide, sunitinib, bevacizumab, interferon-alpha, interferon-beta, 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. 
     
     
         15 . A pegylated peptide consisting of the amino acid sequence selected from the group consisting of SEQ ID NO: 9, 11-13, 26, 32, 67, 80, 82, 1-8, 10, 14-25, 27-31, 33-66, 68-79, 81, and 83-101 or a pharmaceutically acceptable salt thereof. 
     
     
         16 . The peptide in the form of a pharmaceutically acceptable salt of  claim 1 , wherein said peptide is produced by solid phase peptide synthesis or produced by a yeast cell or bacterial cell expression system. 
     
     
         17 . A composition comprising the peptide of  claim 1 , wherein the composition is a pharmaceutical composition and comprises water and a buffer. 
     
     
         18 . The peptide according to  claim 3 , wherein the pharmaceutically acceptable salt is the acetate salt. 
     
     
         19 . The pharmaceutical composition according to  claim 19 , wherein the adjuvant comprises IL-7 and/or IL-15. 
     
     
         20 . A method of treating a patient who has a cancer overexpressing a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 1, 3-6, 8, 10, 14-25, 27-31, 33-66, 68-76, 78, 79, 81, and 84-101, comprising administering to said patient a composition comprising a population of activated T cells that kill the cancer cells,
 wherein the activated T cells are cytotoxic T cells produced by contacting CD8+ T cells with an antigen presenting cell that presents a peptide consisting of the amino acid sequence selected from the group consisting of SEQ ID NO: 1, 3-6, 8, 10, 14-25, 27-31, 33-66, 68-76, 78, 79, 81, and 84-101 in a complex with an WIC class I molecule on the surface of the antigen presenting cell in vitro, for a period of time sufficient to activate said T cell,   wherein said cancer is selected from the group consisting of esophageal cancer, lung cancer, urinary bladder cancer, ovarian cancer, melanoma, uterine cancer, hepatocellular cancer, renal cell cancer, brain cancer, colorectal cancer, breast cancer, gastric cancer, pancreatic cancer, gallbladder cancer, bile duct cancer, prostate cancer, and leukemia.