Systemic efficacy of combined suicide/cytokine gene therapy in a murine model of hepatocellular carcinoma

Background/Aims Gene therapy might be a promising therapeutic approach for advanced hepatocellular carcinoma (HCC) not amenable to any effective traditional treatment. The aim of the study was to evaluate the in vitro and in vivo efficacy of combined gene therapy of HCC with two different MoMLV-derived retroviral vectors, an MFG- and a LXSN-derived vector, both containing HSV-TK and hIL-2. Results In vitro experiments on HCC cells showed efficient killing of transduced cells and efficient bystander effect after ganciclovir (GCV) treatment, with higher antitumor activity when the MFG-based vector was used. In vivo studies in a murine syngenic model of HCC demonstrated that treatment with GCV led to complete regression of tumors composed of transduced cells and regression of distant non-transduced tumors. Tumor transduction and efficacy of treatment was also demonstrated after in vivo delivery of vectors. Microarray analysis of tumor samples in mice receiving gene therapy showed up-regulation of genes involved in immune response and signal transduction. Conclusions We demonstrated the in vitro and in vivo efficacy of combined retroviral-mediated gene therapy for HCC, with significant systemic therapeutic efficacy in vivo.