Novel peptides and combination of peptides for use in immunotherapy against various tumors

Abstract

A method of treating a patient who has hepatocellular carcinoma (HCC), colorectal carcinoma (CRC), glioblastoma (GB), gastric cancer (GC), esophageal cancer, NSCLC, pancreatic cancer (PC), renal cell carcinoma (RCC), benign prostate hyperplasia (BPH), prostate cancer (PCA), ovarian cancer (OC), melanoma, breast cancer (BRCA), CLL, Merkel cell carcinoma (MCC), SCLC, Non-Hodgkin lymphoma (NHL), AML, gallbladder cancer and cholangiocarcinoma (GBC, CCC), urinary bladder cancer (UBC), and uterine cancer (UEC) includes administering to said patient a composition containing a population of activated T cells that selectively recognize cells in the patient that aberrantly express a peptide. A pharmaceutical composition contains activated T cells that selectively recognize cells in a patient that aberrantly express a peptide, and a pharmaceutically acceptable carrier, in which the T cells bind to the peptide in a complex with an MHC class I molecule, and the composition is for treating the patient who has HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC. A method of treating a patient who has HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC includes administering to said patient a composition comprising a peptide in the form of a pharmaceutically acceptable salt, thereby inducing a T-cell response to the HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC.

1 . A peptide consisting of the amino acid sequence KLLAVIHEL (SEQ ID NO: 253) in the form of a pharmaceutically acceptable salt. 
     
     
         2 . The peptide of  claim 1 , wherein said peptide has the ability to bind to an MHC class-I molecule, and wherein said peptide, when bound to said MHC, is capable of being recognized by CD8 T cells. 
     
     
         3 . The peptide of  claim 1 , wherein the pharmaceutically acceptable salt is chloride salt. 
     
     
         4 . The peptide of  claim 1 , wherein the pharmaceutically acceptable salt is acetate salt. 
     
     
         5 . A composition comprising the peptide of  claim 1 , wherein the composition comprises an adjuvant and a pharmaceutically acceptable carrier. 
     
     
         6 . The composition of  claim 5 , wherein the peptide is in the form of a chloride salt. 
     
     
         7 . The composition of  claim 5 , wherein the peptide is in the form of an acetate salt. 
     
     
         8 . The composition of  claim 5  wherein the adjuvant is 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. 
     
     
         9 . The composition of  claim 8 , wherein the adjuvant is IL-2. 
     
     
         10 . The composition of  claim 8 , wherein the adjuvant is IL-7. 
     
     
         11 . The composition of  claim 8 , wherein the adjuvant is IL-12. 
     
     
         12 . The composition of  claim 8 , wherein the adjuvant is IL-15. 
     
     
         13 . The composition of  claim 8 , wherein the adjuvant is IL-21. 
     
     
         14 . A pegylated peptide consisting of the amino acid sequence of KLLAVIHEL (SEQ ID NO: 253) or a pharmaceutically acceptable salt thereof. 
     
     
         15 . The peptide of  claim 14 , wherein the pharmaceutically acceptable salt is chloride salt. 
     
     
         16 . The peptide of  claim 14 , wherein the pharmaceutically acceptable salt is acetate salt. 
     
     
         17 . A composition comprising the pegylated peptide of  claim 14  or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 
     
     
         18 . A peptide consisting of the amino acid sequence of KLLAVIHEL (SEQ ID NO: 253), wherein at least one amino acid of the peptide is a D-amino acid. 
     
     
         19 . 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. 
     
     
         20 . A composition comprising the peptide of  claim 1 , wherein the composition is a pharmaceutical composition and comprises water and a buffer.