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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 预览 被引量:6

An in vitro study on the inhibition of hepatocellular carcinomagrowth by AFP-specific CD8~+ T/ CD4~+ T activated bylentivirally engineered and AFP pulsed DC
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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,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.
作者 刘扬 宋振顺 周波 傅晓辉 吴孟超 Butterfield LH LIU Yang,SONG Zhen-shun,ZHOU Bo,FU Xiao-hui,WU Meng-chao,Butterfield LH (1.Hepatobiliary Surgery Division,Tenth People's Hospital,Tongji University,Shanghai 200072,China;(2.Dept.of Combined Therapy of Tumor,East Hepatobiliary Surgery Hospital,Shanghai 200438,China;(3.Dept.of Surgery and Immunology,Cancer Institute of Pittsburgh University,Pittsburgh 15213,Pennsylvania,USA)
出处 《同济大学学报:医学版》 CAS 2011年第1期 18-23,共6页 Journal of Tongji University(Medical Science)
基金 上海浦江人才计划资助项目(07PJ14004)
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
作者简介 刘扬(1963-),副主任医师,博士后.E—mail:yliu6633@yahoo.com.cn
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参考文献5

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二级参考文献3

  • 1Yang Liu, Sean Daley, Viktoria N. Evdokimova, et al. Hierarchy of alpha fetoprotein (AFP)-specific T cell responses in subjects with AFP-positive hepatocellular cancer[J]. J Immunol,2006,177:712 -721. 被引量:1
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同被引文献86

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