Section for Cancer Immunotherapy, Investigative Treatment Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Chiba, Japan.
Cancer Sci. 2011 Sep;102(9):1622-9. doi: 10.1111/j.1349-7006.2011.02003.x. Epub 2011 Jul 8.
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.
磷脂酰聚糖 3（GPC3）不仅可用作新型肿瘤标志物，还可用作免疫治疗的胎抗原。我们最近从 GPC3（144-152）肽疫苗接种后的肝癌患者中建立了 HLA-A2 限制性 GPC3（144-152）肽特异性 CTL 克隆。本研究旨在评估 HLA-A2 限制性 GPC3（144-152）肽特异性 CTL 克隆对卵巢透明细胞癌（CCC）细胞系的肿瘤反应性。GPC3（144-152）肽特异性 CTL 克隆可通过干扰素（IFN）-γ酶联免疫斑点试验识别 HLA-A2 阳性和 GPC3 阳性卵巢 CCC 细胞系，并对 KOC-7c 细胞表现出细胞毒性。CTL 克隆以 HLA Ⅰ类限制方式识别卵巢 CCC 细胞上天然加工的 GPC3 衍生肽。此外，我们证实 GPC3 的表达水平决定了 CTL 的识别，亚毒性剂量的化疗使肿瘤细胞更容易受到 CTL 细胞毒性的影响。因此，通过将化疗与免疫治疗相结合，可能能够治疗卵巢 CCC 患者。我们的数据表明，GPC3 可能是卵巢 CCC 免疫治疗的有效靶标。
