Novel immunotherapy against neuronal and brain tumors

Abstract

The present invention relates to peptides, 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 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 relates to 11 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.

1 . A nucleic acid encoding a peptide comprising an amino acid sequence that is selected from the group of SEQ ID NO: 1 to SEQ ID NO: 11 wherein the peptide is capable of inducing T cells cross-reacting with the peptide. 
     
     
         2 . The nucleic acid according to  claim 1  which is DNA, cDNA, PNA, CNA, RNA or combinations thereof. 
     
     
         3 . An expression vector capable of expressing a nucleic acid according to  claim 1 . 
     
     
         4 . A host cell comprising a nucleic acid according to  claim 1 . 
     
     
         5 . The host cell according to  claim 4 , wherein the host cell is an antigen presenting cell or a dendritic cell. 
     
     
         6 . A method of producing a peptide comprising an amino acid sequence that is selected from the group of SEQ ID NO: 1 to SEQ ID NO: 11, the method comprising culturing the host cell according to  claim 5  and isolating the peptide from the host cell or its culture medium. 
     
     
         7 . Activated cytotoxic T lymphocytes (CTL), produced by a method 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 the CTL in an antigen specific manner, wherein the antigen is a peptide comprising an amino acid sequence that is selected from the group of SEQ ID NO: 1 to SEQ ID NO: 11, and wherein said CTL selectively recognize a cell aberrantly expressing a polypeptide comprising an amino acid sequence of SEQ ID NO: 1 to SEQ ID NO: 11. 
     
     
         8 . A method of killing target cells in a patient; wherein the target cells aberrantly express a polypeptide comprising an amino acid sequence that is selected from the group of SEQ ID NO: 1 to SEQ ID NO: 11, the method comprising administering to the patient an effective number of cytotoxic T lymphocytes (CTL) as defined in  claim 7 . 
     
     
         9 . The method according to  claim 8 , wherein the target cells are cancer cells 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 (PNET, e.g. medulloblastoma, medulloepithelioma, neuroblastoma, retinoblastoma, ependymoblastoma), tumors of the pineal parenchyma (e.g. pineocytoma, pineoblastoma), ependymal cell tumors, choroid plexus tumors, neuroepithelial tumors of uncertain origin (e.g. gliomatosis cerebri, astroblastoma) or glioblastoma cells. 
     
     
         10 . The nucleic acid according to  claim 1 , wherein the nucleic acid encodes a peptide having an overall length of between 8 and 16 amino acids. 
     
     
         11 . The nucleic acid according to  claim 1 , wherein the nucleic acid encodes a peptide consisting essentially of an amino acid sequence according to SEQ ID NO: 1 to SEQ ID NO: 11. 
     
     
         12 . The activated CTL of  claim 7 , wherein the antigen is a peptide having an overall length of between 8 and 16 amino acids. 
     
     
         13 . The activated CTL of  claim 7 , wherein the antigen is a peptide consisting of an amino acid sequence according to SEQ ID NO: 1. 
     
     
         14 . The activated CTL of  claim 7 , wherein the antigen is a peptide consisting of an amino acid sequence according to SEQ ID NO: 2. 
     
     
         15 . The activated CTL of  claim 7 , wherein the antigen is a peptide consisting of an amino acid sequence according to SEQ ID NO: 3. 
     
     
         16 . The activated CTL of  claim 7 , wherein the antigen is a peptide consisting of an amino acid sequence according to SEQ ID NO: 4. 
     
     
         17 . The activated CTL of  claim 7 , wherein the antigen is a peptide consisting of an amino acid sequence according to SEQ ID NO: 5. 
     
     
         18 . The activated CTL of  claim 7 , wherein the antigen is a peptide consisting of an amino acid sequence according to SEQ ID NO: 6. 
     
     
         19 . The activated CTL of  claim 7 , wherein the antigen is a peptide consisting of an amino acid sequence according to SEQ ID NO: 7. 
     
     
         20 . The activated CTL of  claim 7 , wherein the antigen is a peptide consisting of an amino acid sequence according to SEQ ID NO: 8.