Development of therapeutic cancer vaccine

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Our study clarified several new aspects of the human tumor immune response. 1) Some of IAP (inhibitors of apoptosis proteins) is considered to be candidates for human cancer vaccines. Particularly, HLA-A24 restricted peptide survivin 2B, a splicing variant of survivin gene, is immunogenic in patients with many types of cancer such as colon, pancreas, lung, oral and urogenital origins. It was indicated that patients vaccinated with this peptide could respond well as assessed by peptide-specific tetramer study. 2) The detail of the expression of HLA class I molecule in human cancers is not yet known. To this end, we developed mAb reacting on the paraffin-embeded specimen against all of HLA class I alleles. The data demonstrated that the HLA class I in more than 80 % of breast and prostate cancer was markedly decreased, and this was due to transcriptional regulation by histone deacetylation (HDAC) of the gene expression. Indeed, treatment of HLA class I down-regulated breast cancer lines with HDAC inhibitor could restore its expression on the cell surface. Currently clinical trials with survivin 2B peptide combined with HDAC inhibitor is underway in breast cancer patients. 3) We also clarified tumor antigens selectively expressing in human cancer stem cell (CSC)/cancer-initiating cell (CIC) that was sorted with side population technology. Consequently, we detected five such antigens including novel cell surface molecule. These antigens may be potential candidates for human cancer vaccines, since these are more immunogenic than non CSC/CIC antigens.