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Identification of a WT1 protein‐derived peptide,WT1187, as a HLA‐A*0206‐restricted,WT1‐specific CTL epitope
Authors:Zheyu Li  Yoshihiro Oka  Akihiro Tsuboi  Fumihiro Fujiki  Yukie Harada  Hiroko Nakajima  Tomoki Masuda  Yoko Fukuda  Mai Kawakatsu  Soyoko Morimoto  Takamasa Katagiri  Naoya Tatsumi  Naoki Hosen  Toshiaki Shirakata  Sumiyuki Nishida  Yutaka Kawakami  Keiko Udaka  Ichiro Kawase  Yusuke Oji  Haruo Sugiyama
Institution:1. Functional Diagnostic Science;2. Respiratory Medicine, Allergy and Rheumatic Diseases;3. Cancer Immunotherapy, Osaka University Graduate School of Medicine, Osaka;4. Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo;5. Department of Immunology, Kochi Medical School, Kochi, Japan
Abstract:The Wilms' tumor gene WT1 is overexpressed in various kinds of hematopoietic malignancies as well as solid cancers, and this protein has been demonstrated to be an attractive target antigen for cancer immunotherapy. WT1‐specific CTL epitopes with a restriction of HLA‐A*2402 or HLA‐A*0201 have been already identified. In the present study it has been demonstrated that a 9‐mer WT1‐derived WT1187 peptide, which had already been shown to elicit a WT1‐specific CTL response with a restriction of HLA‐A*0201, can also elicit a CTL response with a restriction of HLA‐A*0206. In all three different HLA‐A*0206+ healthy donors examined, WT1187 peptide‐specific CTL could be generated from peripheral blood mononuclear cells, and the CTL showed cytotoxic activity that depended on dual expression of WT1 and HLA‐A*0206 molecules. The present study describes the first identification of a HLA‐A*0206‐restricted, WT1‐specific CTL epitope. The present results should help to broaden the application of WT1 peptide‐based immunotherapy from only HLA‐A*0201‐positive to HLA‐A*0206‐positive cancer patients as well.
Keywords:cancer  HLA‐A*0206  vaccine  WT1
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