AFP特异性肝癌疫苗抑制肝细胞癌生长

Abstract

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，我们检测了AFP特异性T细胞的体外抗肿瘤免疫活性。方法：我们采用经过AFP抗原决定簇肽刺激或慢病毒转染的树突状细胞(dendritic cells, DC)，活化AFP特异性的CD4+T细胞和CD8+T细胞(肝癌疫苗)，并在体外检测了这群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，为肝细胞癌的临床免疫治疗提供了依据。 Objective: Alpha-fetoprotein (AFP), a tumor-associated antigen for hepatocellular carcinoma (HCC), is an established biomarker for hepatocellular cancer (HCC). In this study, we detected antitumor activity of AFP specific T cells in vitro. Methods: We created a lentivirus expressing AFP (Lenti-AFP) and investigated the antitumor activity of AFP-specific CD4+ and CD8+ T cells(liver tumor vaccines), which were activated by either AFP peptide-pulsed or Lenti-AFP-engineered DC in vitro. Results: Our research demonstrated that the AFP-specific T cells could efficiently kill HepG2 cells, by significantly increasing the level of IL-2, IFN-γ、TNF-α、perforin and granzyme B, as well as by inhibiting the production of IL-10 (a negative regulator of T cell activation). Conclusion: AFP-specific CD4+ and CD8+ T cells (liver tumor vaccines) which were activated by either AFP peptide-pulsed or Lenti-AFP-engineered DC have obviously antitumor activity. This study provides new insight into the design of DC activated antigen-specific T cell-based clinical trials