Identification of immunoglobulin superfamily 11 (IGSF11) as a novel target for cancer immunotherapy of gastrointestinal and hepatocellular carcinomas

Cancer Science - Tập 96 Số 8 - Trang 498-506 - 2005
Takeshi Watanabe1,2,3, Takako Suda4,5,3, Takuya Tsunoda4, Naotaka Uchida4, Katsuaki Ura2, Tatsushi Kato1, Suguru Hasegawa1, Seiji Satoh1, Shigetsugu Ohgi5, Hideaki Tahara4, Yoichi Furukawa2, Yusuke Nakamura2
1Department of Gastroenterological Surgery, Kyoto University Graduate School ofMedicine, 54 Shogoin-Kawaramachi, Sakyo-ku, Kyoto 606-8507
2Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639
3These authors contributed equally to this study
4Department of Surgery and Bioengineering, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639
5Division of Organ Regeneration Surgery, Department of Surgery, Tottori University Faculty of Medicine, 36-1 Nishi-machi, Yonago, Tottori 683-8504, Japan

Tóm tắt

We previously performed gene expression profile analyses of 20 intestinal‐type gastric cancers, and identified a set of genes whose expression levels were elevated in cancer tissues compared to their corresponding non‐cancerous tissues. In the present study we focused on the immunoglobulin superfamily 11 gene (IGSF11). Its expression was also elevated in colorectal cancers and hepatocellular carcinomas as well as intestinal‐type gastric cancers. Northern blot analysis showed that it was expressed abundantly in testis and ovary. These data suggest that IGSF11 is a good candidate of cancer‐testis antigen. Furthermore, suppression of IGSF11 by siRNA retarded the growth of gastric cancer cells. To investigate the possibility of clinical application of peptide vaccine to IGSF11, we synthesized candidate epitope peptides for IGSF11 and tested whether the peptides elicit IGSF11‐specific CTL. As a result, we successfully established oligo‐clonal CTL by stimulation with IGSF11‐9‐207 (ALSSGLYQC). In addition, we also established additional CTL using IGSF11‐9V (ALSSGLYQV), anchor‐modified peptides of IGSF11‐9‐207. These peptides showed IGSF11‐specific cytotoxic activity in an HLA‐A*0201‐restricted fashion, suggesting that these peptides may be applicable for cancer immunotherapy. These findings have provided a novel insight into carcinogenesis of the stomach, colon and liver, and will be helpful for the development of novel therapeutic strategies to a wide range of human cancers. (Cancer Sci 2005; 96: 498 –506)

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Cancer Science

Tập 96 Số 8

498-506

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