• Open Access

Glypican-3 could be an effective target for immunotherapy combined with chemotherapy against ovarian clear cell carcinoma

Authors

  • Shiro Suzuki,

    1. Section for Cancer Immunotherapy, Investigative Treatment Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Chiba
    2. Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya
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  • Toshiaki Yoshikawa,

    1. Section for Cancer Immunotherapy, Investigative Treatment Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Chiba
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  • Tomoya Hirosawa,

    1. Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya
    2. Division of Immunology, Aichi Cancer Center Research Institute, Nagoya
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  • Kiyosumi Shibata,

    1. Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya
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  • Fumitaka Kikkawa,

    1. Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya
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  • Yoshiki Akatsuka,

    1. Division of Immunology, Aichi Cancer Center Research Institute, Nagoya
    2. Department of Hematology and Oncology, Fujita Health University, Aichi, Japan
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  • Tetsuya Nakatsura

    Corresponding author
    1. Section for Cancer Immunotherapy, Investigative Treatment Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Chiba
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To whom correspondence should be addressed.
E-mail: tnakatsu@east.ncc.go.jp

Abstract

Glypican-3 (GPC3) is useful not only as a novel tumor marker, but also as an oncofetal antigen for immunotherapy. We recently established HLA-A2-restricted GPC3144-152 peptide-specific CTL clones from hepatocellular carcinoma patients after GPC3144-152 peptide vaccination. The present study was designed to evaluate the tumor reactivity of a HLA-A2-restricted GPC3144-152 peptide-specific CTL clone against ovarian clear cell carcinoma (CCC) cell lines. The GPC3144-152 peptide-specific CTL clone could recognize HLA-A2-positive and GPC3-positive ovarian CCC cell lines on interferon (IFN)-γ enzyme-linked immunospot assay and showed cytotoxicity against KOC-7c cells. The CTL clone recognized naturally processed GPC3-derived peptide on ovarian CCC cells in a HLA class I-restricted manner. Moreover, we confirmed that the level of GPC3 expression was responsible for CTL recognition and that subtoxic-dose chemotherapy made tumor cells more susceptible to the cytotoxic effect of CTL. Thus, it might be possible to treat ovarian CCC patients by combining chemotherapy with immunotherapy. Our data suggest that GPC3 could be an effective target for immunotherapy against ovarian CCC. (Cancer Sci 2011; 102: 1622–1629)

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