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

通过在肿瘤部位注射 Glypican-3 表位肽进行射频消融预防 HCC 复发

基本信息

批准号：
21591756
负责人：
KOMORI Hiroyuki
金额：
$ 3万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2011
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591756/
关键词：
CTL GPC3 HCC RFA ペプチドワクチン GPC3ペプチド肝細胞癌腫瘍抗原特異的CTL

项目摘要

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.

射频消融（RFA）中将Glypican-3（GPC3）表位肽注射到肝细胞癌（HCC）的肿瘤部位，合理作为辅助免疫疗法，预防刺激树突状细胞治疗后HCC的复发。我们之前报道过GPC3刺激的DC疫苗肽可以抑制GPC3+肿瘤的生长。而且，从 HCC 患者中分离出的 GPC3 特异性 CTL 可以减少植入 NOD/SCID 小鼠体内的 GPC3+人 HCC 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 HCC 患者，包括射频消融 (RFA) 和手术治疗切除。 RFA 后 9 名患者中有 5 名循环 GPC3 特异性 CTL 增加，但手术切除后 9 名患者中只有 1 名增加。RFA 后增加的 GPC3 特异性 CTL 数量明显多于手术切除后。 Nakatsura 和国家癌症中心东部的合作者在第一阶段研究中检查了 GPC3 肽疫苗接种的安全性。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，我们希望确保该策略可能是一种新型辅助免疫疗法，有可能有助于预防 HCC 的出现、进展和/或复发。