AFP特异性CD8^+ T/CD4^+ T肝癌疫苗体外杀伤肝癌细胞的实验研究

An in vitro study on the inhibition of hepatocellular carcinomagrowth by AFP-specific CD8^+ T/ CD4^+ T activated bylentivirally engineered and AFP pulsed DC

目的甲胎蛋白作为一种肿瘤特异性抗原,是临床上诊断肝癌的重要指标。本研究中,检测AFP特异性T细胞的体外抗肿瘤免疫活性。方法采用经过AFP抗原决定簇肽刺激或慢病毒转染的的树突状细胞(dendriticcells,DC),活化AFP特异性的CD4+T细胞和CD8+T细胞,并在体外检测这群T细胞对人肝癌细胞HepG2的杀伤活性。结果本研究结果显示,AFP特异性的CD4+T细胞和CD8+T细胞体外能有效杀伤HepG2细胞,上调培养体系中IL-2、IFN-γ、TNF-α、穿孔素、颗粒酶的水平,对于T细胞活化的负调控因子IL-10,具有显著的抑制作用。结论经DC活化后的AFP特异性T细胞具有显著的体外抗肿瘤免疫活性,有望成为肝细胞癌的免疫治疗新方法。

Objective To study the inhibition of hepatocellular carcinoma growth by AFP-specific CD8＋ T/ CD4＋ T activated by lentivirally engineered and AFP pulsed DC in vitro.Methods In this study,a lentivirus expressing the AFP antigen was created.AFP-specific CD4＋ and CD8＋ T cells were then activated by either AFP peptide-pulsed or lenti-AFP-engineered methods its inhibitory effect on HCC was carried out in vitro.Results AFP-specific T cells could efficiently kill HepG2 cells,significantly increasing the levels of IL-2,IFN-γ、TNF-α、perforin and granzyme B,as well as inhibiting the production of IL-10（anegative regulator of T cell activation）.Conclusion AFP-specific CD4＋ and CD8＋ T cells,which were activated by either AFP peptide-pulsed or lenti-AFP-engineered DC,have obvious antitumor activity.This study provides a new insight into the design of DC activated antigen-specific T cell-based clinical trials.