Prevention of HCC recurrence by Radiofrequency ablation with Glypican-3 epitope peptide injection to tumor site

肝细胞癌（Hepatocellular carcinoma，HCC）射频消融术（Radiofiltration ablation，RFA）中，将磷脂酰肌醇蛋白聚糖-3（Glypican-3，GPC 3）表位肽段注射到肿瘤部位，可作为一种辅助免疫治疗，预防DC治疗后HCC的复发。从肝癌患者中分离的GPC 3特异性CTL也可以抑制植入NOD/SCID小鼠的GPC 3+人肝癌肿瘤细胞系的生长。Nakatura T等人前瞻性研究了接受局部治疗的肝癌患者，包括射频消融（RFA）和手术切除。RFA后9例患者中有5例患者循环中GPC 3特异性CTL增加，而手术切除后仅1例患者循环中GPC 3特异性CTL增加，RFA后GPC 3特异性CTL增加的数量明显多于手术切除后。GPC 3肽疫苗接种的安全性在1期研究中由Nakatelo和国家癌症中心东部的合作者进行了检查。我们将尝试检查从RFA到将表位肽注射到肿瘤部位的更有效的间隔时间，以及更有效的剂量。在临床研究中，我们希望确定这种策略可能是一种新的辅助免疫治疗，可能有助于预防HCC的出现，进展和/或复发。

Injection of Glypican-3(GPC3) epitope peptide to tumor site of Hepatocellular carcinoma(HCC) in Radiofrequency ablation(RFA) reasonable to be adjuvant immunotherapy preventing recurrence of HCC after treatment with stimulating dendritic cells.We previously reported that DC vaccine stimulated by GPC3 peptide could suppress the GPC3+tumor growth. And also GPC3 specific CTLs, isolated from HCC patients, could reduce growth of GPC3+human HCC tumor cell line implanted into NOD/SCID mouse.Nakatura T et al studied prospectively HCC patients treated with locoregional therapies, including radiofrequency ablation(RFA) and surgical resection. Circulating GPC3-specific CTLs were increased in 5 of 9 patients after RFA, but in only 1 of 9 patients after surgical resection.The number of increased GPC3-specific CTLs after RFA was significantly larger than that after surgical resection. The safety of GPC3 peptide vaccination was checked in phase 1 study by Nakatsura and collaborators at National Cancer Center East. We will try to check the more effective interval time from RFA to injection epitope peptide into tumor site, and more effective doze of that. In clinical study, we want to make sure this strategy may be a novel adjuvant immunotherapy that can potentially help to prevent the appearance, advance and/or recurrence of HCC.