Basic study of gene therapy for hepatocellular carcinoma

目前，正在进行用逆转录病毒载体生产细胞进行自杀基因转移以治疗脑肿瘤的临床试验。方法：用逆转录病毒介导的单纯疱疹病毒胸苷激酶（HSV-TK）基因转染5株肝癌细胞，检测其对更昔洛韦的敏感性。将不同群体的HSV-TK转导的HuH 7细胞皮下注射到具有未转导的HuH 7细胞的无胸腺裸鼠中以分析“旁观者”效应。结果：5个肝癌细胞系用病毒上清转导，除1个外，其余50个转导克隆均对更昔洛韦敏感。当接种物由少至10%的含HSV-TK的转导细胞组成时，30个肿瘤中有21个发生完全消退。生产细胞注射组和GCV治疗组的肿瘤体积明显小于GCV治疗组（p<0.01）。结论：该基因治疗方法可能是治疗人肝癌的有效方法。

Currently, clinical trials of suicide gene transfer with retroviral vector producer cells are being carried out for the treatment of brain tumors. The feasibility of applying this approach for the treatment of hepatocellular carcinoma is studied.Methods : Five hepatoma cell lines were tested for retroviral mediated transduction efficiency with the herpes simplex thymidine kinase (HSV-TK) gene and for the induced drug sensitivity to ganciclovir. Different populations of HSV-TK transduced HuH7 cells were subcutaneously injected into athymic nude mice with non transduced HuH7 cells to analyze the "bystander" effect. The retroviral vector producer cells were intratumorally injected into pre-established HuH7 tumors to study the antitumor effect.Results : Five hepatoma cell lines were transduced with the viral supernatant, and all resultant 50 transduced clones, except one, were sensitive to ganciclovir. Complete regression occurred in 21 out of 30 tumors when the inoculum consisted of as few as 10% of HSV-TK containing transduced cells. The producer cell injection into tumors and GCV treatment group was significantly smaller in size of the tumors compared to GCV treatment group (p<0.01).Conclusions : This gene therapy approach could potentially be effective for the treatment of human hepatocellular carcinoma.