Peptides, combination of peptides, and cell based medicaments for use in immunotherapy against urinary bladder 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 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 2-149, wherein the peptide comprises from 9 to 20 amino acids. 
     
     
         2 . The peptide of  claim 1 , wherein said peptide has the ability to bind to an MHC class-I or -II molecule, and wherein said peptide, when bound to said MHC, is capable of being recognized by CD4 and/or CD8 T cells. 
     
     
         3 . The peptide of  claim 1 , wherein the peptide is in the form of a pharmaceutically acceptable salt. 
     
     
         4 . The peptide of  claim 3 , wherein the pharmaceutically acceptable salt is chloride salt or acetate salt. 
     
     
         5 . The peptide of  claim 1 , wherein the peptide consists of the amino acid sequence selected from the group consisting of SEQ ID NOs: 2-149. 
     
     
         6 . A fusion protein comprising the peptide of  claim 1  and N-terminal amino acids of the HLA-DR antigen-associated invariant chain (Ii). 
     
     
         7 . A fusion protein comprising the peptide of  claim 1  and an antibody. 
     
     
         8 . The fusion protein of  claim 8 , wherein the antibody binds to an dendritic cell. 
     
     
         9 . A pharmaceutical composition comprising the peptide of  claim 1 . 
     
     
         10 . The pharmaceutical composition of  claim 9 , further comprising an adjuvant. 
     
     
         11 . The pharmaceutical composition of  claim 10 , wherein the adjuvant is selected from 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. 
     
     
         12 . A modified peptide comprising the peptide of  claim 1 , wherein said peptide comprises at least one non-peptide bond or at least one D-amino acid. 
     
     
         13 . An in vitro method for producing activated T lymphocytes, comprising contacting in vitro T cells with antigen loaded human HLA-A*02:01 expressed on the surface of a suitable antigen-presenting cell or an artificial construct mimicking an antigen-presenting cell for a period of time sufficient to activate said T cells in an antigen specific manner, wherein said antigen is a peptide consisting of the amino acid sequence selected from the group consisting of SEQ ID NOs: 2-149. 
     
     
         14 . A method for producing a peptide consisting of the amino acid sequence selected from the group consisting of SEQ ID NOs: 2-149, comprising culturing a host cell, and isolating the peptide from said host cell and/or culture medium thereof. 
     
     
         15 . A method for killing target cells in a patient who has cancer, wherein the target cells present a peptide consisting of the amino acid sequence selected from the group consisting of SEQ ID NOs: 2-149 in a complex with HLA-A*02:01, comprising administering to the patient the activated T cells produced by the method of  claim 13 ,
 wherein said cancer is selected from the group of esophageal cancer, pancreatic cancer, gallbladder cancer, uterine cancer, head and neck squamous cell carcinoma, and bile duct cancer.   
     
     
         16 . A kit comprising:
 a) a container comprising the pharmaceutical composition according to  claim 9  in solution or in lyophilized form;   b) optionally, a second container containing a diluent or reconstituting solution for the lyophilized formulation;   c) optionally, instructions for (i) use of the solution or (ii) reconstitution and/or use of the lyophilized formulation.   
     
     
         17 . The kit according to  claim 16 , further comprising one or more of (iii) a buffer, (iv) a diluent, (v) a filter, (vi) a needle, or (v) a syringe. 
     
     
         18 . The pharmaceutical composition of  claim 10 , wherein the adjuvant is selected from the group consisting of IL-2, IL-12, and IL-15. 
     
     
         19 . The pharmaceutical composition of  claim 10 , further comprising a pharmaceutically acceptable carrier. 
     
     
         20 . The pharmaceutical composition of  claim 10 , further comprising a pharmaceutically acceptable stabilizer.