Novel peptides and combination of peptides as targets or active ingredients for use in immunotherapy against aml 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 of SEQ ID NO: 52, 12, 36, 42, 96, 165, 16, 176, 1-11, 13-15, 17-35, 37-41, 43-51, 53-95, 97-164, 166-175, or 177-198 in the form of a pharmaceutically acceptable salt. 
     
     
         2 . A modified peptide consisting of the amino acid sequence of SEQ ID NO: 52, 12, 36, 42, 96, 165, 16, 176, 1-11, 13-15, 17-35, 37-41, 43-51, 53-95, 97-164, 166-175, or 177-198 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 of SEQ ID NO: 52, 12, 36, 42, 96, 165, 16, 176, 1-11, 13-15, 17-35, 37-41, 43-51, 53-95, 97-164, 166-175, or 177-198 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. 
     
     
         20 . A method of eliciting an immune response in a patient who has cancer, comprising administering to the patient a population of activated T cells that kill the cancer cells which present a peptide consisting of the amino acid sequence of SEQ ID NO: 1-11, 13-15, 17-35, 37-41, 43-51, 53-95, 97-164, 166-175, or 177-198, wherein the activated T cells are cytotoxic T cells produced by in vitro 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, wherein the cancer is selected from the group consisting of acute myelogenous leukemia/acute myeloid leukemia, bile duct cancer, brain cancer, breast cancer, chronic lymphocytic leukemia, colon or rectum cancer, esophageal cancer, gallbladder cancer, liver cancer, melanoma, non-Hodgkin lymphoma, non-small cell lung cancer, ovarian cancer, pancreatic cancer, prostate cancer, kidney cancer, small cell lung cancer, urinary bladder cancer, and uterine cancer.