Basic study of gene therapy for hepatocellular carcinoma

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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.