Glypican-3 could be an effective target for immunotherapy combined with chemotherapy against ovarian clear cell carcinoma
Glypican-3 could be an effective target for immunotherapy combined with chemotherapy against ovarian clear cell carcinoma
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DOI：
10.1111/j.1349-7006.2011.02003.x
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发表时间：
2011-09-01
期刊：
影响因子：
5.7
通讯作者：
Nakatsura, Tetsuya
中科院分区：
文献类型：
--
作者：
Suzuki, Shiro;Yoshikawa, Toshiaki;Nakatsura, Tetsuya
GPC3不仅可作为一种新的肿瘤标志物，还可作为一种肿瘤胎儿抗原用于免疫治疗。我们最近在肝细胞癌患者接种GPC3(144-152)多肽疫苗后，建立了人类白细胞抗原A2限制性的GPC3(144-152)多肽特异性CTL克隆。本研究旨在评价人类白细胞抗原A2限制性GPC3(144-152)多肽特异性CTL克隆对卵巢透明细胞癌(CCC)细胞株的抗肿瘤活性。GPC3(144-152)肽特异性CTL克隆在干扰素-γ免疫斑点试验中能够识别HLAA2阳性和GPC3阳性的卵巢CCC细胞系，并显示对KOC-7c细胞的杀伤作用。该CTL克隆以HLAI类限制性方式识别卵巢CCC细胞上天然加工的GPC3衍生肽。此外，我们证实GPC3的表达水平与CTL识别有关，亚毒剂量化疗使肿瘤细胞更容易受到CTL的细胞毒作用的影响。因此，通过化疗和免疫治疗相结合的方法来治疗卵巢CCC是可能的。我们的数据表明，GPC3可能是卵巢CCC免疫治疗的有效靶点。(《癌症科学》2011年；第102期：16221629页)
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)-gamma 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: 16221629)