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  • 刘扬,宋振顺,周波,等.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[J].同济大学学报(医学版),2011,32(1):18-23.    [点击复制]
  • LIU Yang,SONG Zhen-shun,ZHOU Bo,et al.An in vitro study on the inhibition of hepatocellular carcinoma growth by AFP-specific CD8+T/CD4+T activated by lentivirally engineered and AFP pulsed DC[J].同济大学学报(医学版),2011,32(1):18-23.   [点击复制]
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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
刘扬1,宋振顺1,周波1,傅晓辉2,吴孟超2,ButterfieldLH3
0
(1. 同济大学附属第十人民医院肝胆外科,上海 200072

;2. 上海东方肝胆外科医院肿瘤综合治疗科,上海 200433;3. 美国匹兹堡大学肿瘤研究所外科及免疫学组,美国匹兹堡 15213)
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。
关键词:  甲胎蛋白  树突状细胞  细胞因子  AFP特异性  T细胞
DOI:10.3969/j.issn1008-0392.2011.01.018
基金项目:上海浦江人才计划资助项目(07PJ14004)
An in vitro study on the inhibition of hepatocellular carcinoma growth by AFP-specific CD8+T/CD4+T activated by lentivirally engineered and AFP pulsed DC
LIU Yang1,SONG Zhen-shun1,ZHOU Bo1,FU Xiao-hui2,WU Meng-chao2,Butterfield LH3
(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;3.Dept.of Surgery and Immunology,Cancer Institute of Pittsburgh University,Pittsburgh 15213,Pennsylvania,USA)
Abstract:
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.
Key words:  alpha-fetoprotein(AFP)  dendritic cell  cytokine  AFP-specific T cells

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