Novel peptides and combination of peptides for use in immunotherapy against hepatocellular carcinoma (hcc) 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. In particular, the present invention relates to several novel peptide sequences and their variants derived from HLA class I and class II molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses or as targets for the development of pharmaceutically/immunologically active compounds and cells.

1 . A method of treating a patient who has cancer, comprising administering to the patient an effective amount of an antibody specifically binding to an MHC class I or II molecule complexed with a HLA-restricted antigen consisting of the amino acid sequence of GVYDGEEHSV (SEQ ID NO: 303), wherein the cancer is selected from the group consisting of liver cancer, brain cancer, kidney cancer, pancreatic cancer, colon or rectal cancer, leukemia, multiple myeloma, and head and neck squamous cell carcinoma. 
     
     
         2 . The method of  claim 1 , wherein the antibody is a polyclonal antibody, a monoclonal antibody, or a chimeric antibody. 
     
     
         3 . The method of  claim 1 , wherein the antibody binds to the HLA-restricted antigen with a binding affinity of below 20 nanomolar. 
     
     
         4 . The method of  claim 1 , wherein the antibody binds to the MHC class I molecule complexed with the HLA-restricted antigen. 
     
     
         5 . The method of  claim 1 , wherein the antibody is humanized. 
     
     
         6 . The method of  claim 1 , wherein the effective amount of the antibody is from about 1 mg/kg to about 100 mg/kg of body weight per day. 
     
     
         7 . The method of  claim 1 , wherein the antibody is conjugated with a toxin. 
     
     
         8 . A method of diagnosing cancer in a subject, comprising
 administering to the subject an antibody specifically binding to an MHC class I or II molecule complexed with a HLA-restricted antigen consisting of the amino acid sequence of GVYDGEEHSV (SEQ ID NO: 303),
 wherein the antibody is labeled with a radionucleotide, 
   detecting the radionucleotide, and   localizing the cancer using immunoscintiography, wherein the cancer is selected from the group consisting of liver cancer, brain cancer, kidney cancer, pancreatic cancer, colon or rectal cancer, leukemia, multiple myeloma, and head and neck squamous cell carcinoma.   
     
     
         9 . The method of  claim 8 , wherein the antibody is a polyclonal antibody, a monoclonal antibody, or a chimeric antibody. 
     
     
         10 . The method of  claim 8 , wherein the antibody has an affinity value (Kd) of less than 1×10 μM. 
     
     
         11 . The method of  claim 8 , wherein the antibody binds to the MHC class I molecule complexed with the HLA-restricted antigen. 
     
     
         12 . The method of  claim 8 , wherein the antibody is humanized. 
     
     
         13 . The method of  claim 8 , wherein the radionucleotide is selected from the group consisting of  111 In,  99 Tc,  14 C,  131 I,  3 H,  32 P, and  35 S. 
     
     
         14 . The method of  claim 8 , wherein the immunoscintiography is positron emission tomography. 
     
     
         15 . The method of  claim 1 , wherein the cancer is multiple myeloma or head and neck squamous cell carcinoma. 
     
     
         16 . The method of  claim 8 , wherein the cancer is multiple myeloma or head and neck squamous cell carcinoma. 
     
     
         17 . A method for producing an antibody specifically binding to a human major histocompatibility complex (MHC) class I or II molecule complexed with an HLA-restricted antigen consisting of the amino acid sequence of GVYDGEEHSV (SEQ ID NO: 303), comprising
 immunizing a genetically engineered non-human mammal comprising cells expressing said MHC class I or II molecule with a soluble form of an MHC class I or II molecule complexed with said HLA-restricted antigen,   isolating mRNA molecules from antibody producing cells of said non-human mammal,   producing a phage display library displaying protein molecules encoded by said mRNA molecules, and   isolating at least one phage from said phage display library,
 wherein said at least one phage displays said antibody specifically binding to said MHC class I or II molecule complexed with said HLA-restricted antigen. 
   
     
     
         18 . The method of  claim 17 , wherein the antibody is a polyclonal antibody, a monoclonal antibody, or a chimeric antibody. 
     
     
         19 . The method of  claim 17 , wherein the antibody binds to the HLA-restricted antigen with a binding affinity of below 20 nanomolar. 
     
     
         20 . The method of  claim 17 , wherein the antibody binds to the MHC class I molecule complexed with the HLA-restricted antigen.