anti-EGFR-iRGD蛋白介导的PD-1敲除的T细胞治疗胃癌腹腔播散转移

Peritoneal dissemination is the main significant prognostic factor for survival in gastric cancer patients, but there is limited effective therapeutic methods. Based on our previous studies about bispecific recombinant protein anti-EGFR-iRGD which were supported by the National Natural Science Foundation of China, this project aims to provide a comprehensive treatment which contains CRISPR-Cas9 mediated PD-1 disruption of antigen-specific CTL, local radiotherapy mediated tumor environment and upregulated EGFR, tumor penetrating fusion protein targeting for gastric cancer peritoneal carcinomatosis. The aim of this project is to provide a new mode of immune-radiotherapy for clinical application.

胃癌的腹腔播散转移是威胁患者生命最严重且应对手段匮乏的临床难题。申请人在前期成功构建和纯化了兼具高穿透性及肿瘤靶向性融合蛋白anti-EGFR-iRGD的基础上，以胃癌腹腔播散转移模型为对象，通过采用CRISPR-Cas9技术敲除活化的CTL细胞中PD-1分子（CRISPR-Cas9 sgRNA hPD-1 T）以逆转免疫耐受；通过anti-EGFR-iRGD的负载使其获得针对表达EGFR胃癌细胞的靶向性；通过低剂量放疗改善肿瘤免疫微环境及上调肿瘤细胞EGFR的表达。由此建立一种集上述三项关键技术于一体的新型免疫-放疗新模式，评估这种新的治疗模式在胃癌腹腔转移播散治疗中的价值，为可能的临床应用提供科学依据。

胃癌的腹腔播散转移是威胁患者生命最严重且应对手段匮乏的临床难题。申请人在前期成功构建和纯化了兼具高穿透性及肿瘤靶向性融合蛋白anti-EGFR-iRGD的基础上，以胃癌腹腔播散转移模型为对象，通过采用CRISPR-Cas9技术敲除活化的CTL细胞中PD-1分子（CRISPR-Cas9 sgRNA hPD-1 T）以逆转免疫耐受；通过iRGD的负载使其获得针对胃癌细胞的靶向性；由此建立一种集上述关键技术于一体的新型免疫新模式，经过评估这种新的治疗模式在胃癌腹腔转移播散治疗中具有较好的应用价值。相关研究成果发表在Nature Communications，为可能的临床应用提供科学依据。