Novel and powerful mhc-class ii peptides derived from survivin

Abstract

The present invention relates to peptides, nucleic acids, and cells for use in the immunotherapy of cancer. The present invention furthermore relates to survivin-derived tumor-associated cytotoxic T cell (CTL) peptide epitopes, alone or in combination with other tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses. The present invention specifically relates to three novel peptide sequences and variants thereof 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.

1 . A peptide consisting of SEQ ID NO: 22, or a variant thereof that is at least 95% homologous to SEQ ID NO: 22. 
     
     
         2 . The peptide or variant thereof according to  claim 1 , wherein said peptide or variant thereof maintains the ability to bind to a molecule of the human major histocompatibility complex (MHC)-II, and wherein said peptide is capable of stimulating CD4 T cells. 
     
     
         3 . A pharmaceutical composition, comprising the peptide according to  claim 1 . 
     
     
         4 . The pharmaceutical composition according to  claim 3 , wherein said pharmaceutical composition is an anti-cancer vaccine. 
     
     
         5 . The pharmaceutical composition according to  claim 4 , wherein said cancer is selected from astrocytoma, pilocytic astrocytoma, dysembryoplastic neuroepithelial tumor, oligodendrogliomas, ependymoma, glioblastoma multiforme, mixed gliomas, oligoastrocytomas, medulloblastoma, retinoblastoma, neuroblastoma, germinoma, teratoma, gangliogliomas, gangliocytoma, central gangliocytoma, primitive neuroectodermal tumors, medulloblastoma, medulloepithelioma, neuroblastoma, retinoblastoma, ependymoblastoma, tumors of the pineal parenchyma, pineocytoma, pineoblastoma, ependymal cell tumors, choroid plexus tumors, neuroepithelial tumors of uncertain origin, gliomatosis cerebri, astroblastoma, glioblastoma prostate tumor, breast cancer, esophageal cancer, colon cancer, colorectal cancer, renal cell carcinoma, clear cell renal cell carcinoma, lung cancer, CNS, ovarian, melanoma pancreatic cancer, squamous cell carcinoma, leukemia and medulloblastoma, and other tumors or cancers showing an overexpression of Survivin or Neurocan. 
     
     
         6 . The pharmaceutical composition according to  claim 3 , further comprising at least one peptide selected from the group consisting of the peptides according to SEQ ID NOS: 4 to 13 and 24. 
     
     
         7 . The pharmaceutical composition according to  claim 3 , further comprising at least one peptide selected from the group consisting of the peptides according to SEQ ID NOS: 4, 8, 11, 12, 15 and 24. 
     
     
         8 . A kit, comprising:
 (a) a container that contains a pharmaceutical composition containing a peptide according to  claim 1  in solution or in lyophilized form;   (b) optionally, a second container containing a diluent or reconstituting solution for the lyophilized formulation;   (c) optionally, at least one peptide selected from the group consisting of the peptides according to SEQ ID NOS: 1 to 21, 23, and 24; and   (d) optionally, instructions for the use of the solution and/or the reconstitution and/or use of the lyophilized formulation.   
     
     
         9 . A fusion protein comprising a peptide consisting of SEQ ID NO: 22, or a variant thereof that is at least 95% homologous to SEQ ID NO: 22, linked to the N-terminal amino acids of the HLA-DR antigen-associated invariant chain (Ii). 
     
     
         10 . A nucleic acid, encoding for a peptide according to  claim 1 . 
     
     
         11 . A pharmaceutical composition, comprising the nucleic acid according to  claim 10 . 
     
     
         12 . The pharmaceutical composition according to  claim 10 , which is an anti-cancer vaccine. 
     
     
         13 . An expression vector comprising the nucleic acid of  claim 10 . 
     
     
         14 . A host cell, comprising the nucleic acid or the expression vector according to  claim 13 , wherein said host cell is an antigen presenting cell. 
     
     
         15 . A method for producing a peptide consisting of SEQ ID NO: 22, or a variant thereof that is at least 95% homologous to SEQ ID NO: 22, the method comprising culturing the host cell according to  claim 14  under conditions sufficient for the cell to express the nucleic acid, and isolating the peptide from the host cell or its culture medium. 
     
     
         16 . An in vitro method for producing activated cytotoxic T lymphocytes (CTL), comprising contacting in vitro CTL with antigen loaded human class I or II MHC molecules 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 CTL in an antigen specific manner, wherein said antigen is a peptide according to  claim 1 . 
     
     
         17 . An antibody that is specific against a peptide according to SEQ ID NO: 22 when complexed with a respective HLA-molecule.