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研究発表を行った学会；
・第７１回日本癌学会学術総会
　２０１２年　９月１９日〜２１日（札幌）

タイトル；CDCA1- and KIF20A-derived promiscuous HLA class II-restricted Th1 cell epitopes can induce CTLs as well as Th1 cells.

発表者；冨田　雄介　氏
　　　（熊本大学　大学院生命科学研究部 免疫識別学分野）
Abstract；
　We recently identified highly immunogenic cytotoxic T lymphocyte (CTL) epitopes derived from novel tumor-associated antigens, cell division cycle associated 1 (CDCA1), which was overexpressed in various malignancies, but not in many normal organs, by using cDNA microarray analyses. It is well known that CD4+ helper T (Th) cells and CTLs play an essential role in antitumor cellular immunity. Thus, we attempted to identify single polypeptide containing epitopes for both CTL and Th cells that can induce both of them. We successfully identified CDCA1-derived and promiscuous HLA class II-restricted Th cell epitopes naturally containing CTL epitopes that can stimulate Th1-polarized CDCA1-specific T cell restricted by several HLA-DR and DP molecules frequently observed in the Japanese population. These Th1 cells induced by the peptides responded to recombinant CDCA1 protein in the presence of dendritic cells (DC) indicating that this Th1 cell epitope can be naturally processed in DC. In addition, one of these Th1 epitopes induced CDCA1-specific Th cells in vivo in HLA-DR4 transgenic mice (Tgm). Interestingly, these Th1 epitopes containing CTL epitopes were cross-presented to CDCA1-specific CTLs both in vitro human culture system and in HLA-A2 Tgm in vivo. Furthermore, stimulation of PBMC with both CDCA1-derived CTL epitopes and CDCA1-derived Th-cell epitope in the presence of CDCA1-specific Th clone markedly enhanced the induction of CDCA1-specific HLA-A2-restricted CTLs compared with stimulation of PBMC with the CTL epitope alone. These results indicate a potential synergistic effect of immunotherapy using CDCA1-specific Th epitope together with CTL-epitopes. Taken together, CDCA1 Th epitopes in combination with CTL-epitopes are suggested to be applicable for immunotherapy of various cancer patients.