AFP Specific Liver Tumor Vaccines Inhibit Hepatocellular Carcinoma Growth

作者: 刘扬 :同济大学附属第十人民医院肝胆外科; 王跃如 :上海交通大学附属第一人民医院内科; Lisa H Butterfield :美国匹兹堡大学肿瘤研究所;

关键词: 甲胎蛋白树突状细胞细胞因子AFP特异性T细胞Alpha-Fetoprotein (AFP) Dendritic Cell Cytokine AFP-Specific T Cells

摘要: 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-2IFN-γTNF-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: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。

Abstract: 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-γTNF-αperforin 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

文章引用: 刘扬 , 王跃如 , Lisa H Butterfield (2012) AFP特异性肝癌疫苗抑制肝细胞癌生长。 外科, 1, 11-17. doi: 10.12677/HJS.2012.13003


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