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

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 GPC3(144-152) peptide-specific CTL clones from hepatocellular carcinoma patients after GPC3(144-152) peptide vaccination. The present study was designed to evaluate the tumor reactivity of a HLA-A2-restricted GPC3(144-152) peptide-specific CTL clone against ovarian clear cell carcinoma (CCC) cell lines. The GPC3(144-152) 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.