重组腺相关病毒介导HLA-A2基因转导肝癌细胞增强杀伤性T细胞抗肿瘤免疫应答  

Improvement of cytotoxic T lymphocyte anti-tumor immune response by recombinant adeno-associated virus mediated HLA-A2 gene transduction of hepatocellular carcinoma cells

作　　者：周军[1] 马萍[2] 李钧[1] 宋伟[1] 

机构地区：[1]山东大学附属省立医院肿瘤微创综合治疗科,济南250021 [2]山东大学附属省立医院眼科

出　　处：《中华生物医学工程杂志》2017年第2期117-121,共5页Chinese Journal of Biomedical Engineering

摘　　要：目的 本研究旨在探讨重组腺相关病毒（rAAV）介导HLA-A2基因转导肝癌细胞增强杀伤性T细胞（CTL）抗肝癌免疫应答.方法 利用携带人类甲胎蛋白（AFP）基因的rAAV（rAAV-AFP）转导人树突状细胞（DC）体外诱导AFP特异性抗肝癌CTL免疫应答.利用携带人类HLA-A2基因的rAAV（rAAV-HLA-A2）体外转导肝癌细胞提高HLA-A2分子表达水平,增强肝癌细胞对rAAV-AFP转导DC疫苗诱导的AFP特异性CTL免疫反应的敏感性.结果 rAAV-AFP转导DC疫苗能够有效诱导AFP特异性抗肝癌CTL免疫应答.rAAV-HLA-A2能够提高肝癌细胞HLA-A2分子表达,并增强肝癌细胞对rAAV-AFP转导DC疫苗诱导的CTL免疫反应的敏感性.结论 通过rAAV-HLA-A2提高肝癌细胞HLA-A2分子表达是增强CTL抗肝癌免疫应答的有效途径.为AFP表达阳性但HLA-class I分子表达低下的肝癌患者的主动性免疫治疗提供了新的解决方案.Objective To investigate the improvement of cytotoxic T lymphocyte（CTL）anti-tumor immune response by recombinant adeno-associated virus（rAAV）mediated HLA-A2 gene transduction of hepatocellular carcinoma cells. Methods The AFP specific CTL anti-hepatocarcinoma response was induced by rAAV carrying human alpha fetoprotein（AFP）gene（rAAV-AFP）transduction of human dendritic cells（DC） in vitro. The rAAV carrying human HLA-A2 gene（rAAV-HLA-A2）was used to transduce hepatocellular carcinoma cells to improve the expression level of HLA-A2 molecules in vitro and enhance the sensitivity of hepatoma cells to rAAV-AFP transduced DC vaccine-induced AFP-specific CTL immunoreaction. Results rAAV-AFP transduced DC vaccine could effectively induce AFP-specific anti-hepatocarcinoma CTL immune response. rAAV-HLA-A2 can increase the expression of HLA-A2 molecules in hepatocellular carcinoma cells and enhance the sensitivity of hepatocellular carcinoma cells to rAAV-AFP transduced DC vaccine-induced CTL immunoreaction. Conclusion Increasing the expression of HLA-A2 molecules in hepatocellular carcinoma cells by rAAV-HLA-A2 is an effective way to enhance the immune response of CTL against hepatocellular carcinoma , which provides a new solution for active immunotherapy for hepatocellular carcinoma patients with positive AFP expression but with low HLA-class I molecular expression.

关 键 词：腺病毒科 甲胎蛋白类 树突细胞 肝肿瘤 人类白细胞抗原-A2 human leukocyte antigen-A2 

分 类 号：R735.7[医药卫生—肿瘤]