作　　者： (周军）; (马萍）; (李钧）; (宋伟）;

机构地区： 山东大学附属省立医院肿瘤微创综合治疗科, 济南,250021

出　　处： 《中华生物医学工程杂志》

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.

分 类 号： [Z1]