[Generation of HER2 specific, HLA-A24 restricted CTLs derived from gastric cancer patients]
Kousaku Mimura1, Koji Kono, Hidemitsu Sugai
1First Dept. of Surgery, Yamanashi University.
Cancer vaccine therapy is one of the new treatment modalities for gastric cancer at the advanced stage. In this study, we have identified HER2 peptide epitopes restricted by HLA-A24, which is one of the most common alleles in Japanese. We generated immature DCs from PBMCs in a HLA-A24+, HER2+ gastric cancer patient. Immature DCs were co-incubated with irradiated PC-9 cell line, and then autologous PBMCs were co-incubated with PC-9-derived antigen-loaded DCs. As a result, we were able to generate HER2 reactive, HLA-A24-restricted CTL lines. The CTL's specificity was evaluated with ELISPOT analysis and cytotoxic assay. The CTLs specifically recognized cancer cells expressing HLA-A24 and HER2. We synthesized a set of HLA-A24 binding, HER2-derived peptides to identify HLA-A24 restricted peptide epitopes derived from HER2. In conclusion, we were able to identified HER2 peptide epitopes restricted by HLA-A24, suggesting that these epitopes will be new targets for cancer vaccine therapy.
Cancer vaccine therapy is one of the new treatment modalities for gastric cancer at the advanced stage. In this study, we have identified HER2 peptide epitopes restricted by HLA-A24, which is one of the most common alleles in Japanese. We generated immature DCs from PBMCs in a HLA-A24+, HER2+ gastric cancer patient. Immature DCs were co-incubated with irradiated PC-9 cell line, and then autologous PBMCs were co-incubated with PC-9-derived antigen-loaded DCs. As a result, we were able to generate HER2 reactive, HLA-A24-restricted CTL lines. The CTL's specificity was evaluated with ELISPOT analysis and cytotoxic assay. The CTLs specifically recognized cancer cells expressing HLA-A24 and HER2. We synthesized a set of HLA-A24 binding, HER2-derived peptides to identify HLA-A24 restricted peptide epitopes derived from HER2. In conclusion, we were able to identified HER2 peptide epitopes restricted by HLA-A24, suggesting that these epitopes will be new targets for cancer vaccine therapy.
