Construction of retroviral vectors to induce strong hepatoma cell-specific expression of cytokine genes.

Continuing advances in molecular biology have provided tools for a promising approach to the treatment of cancer. Among the various strategies of gene therapy for cancer, many are aimed at killing tumour cells indirectly by the induction or reinforcement of a host immune response by gene transduction of various cytokines, major histocompatibility complex or immune accessory molecules. In the present study, we selected the tumour necrosis factor-alpha, interleukin-2 and interleukin-3 genes as potential cytokine genes to induce antitumour effects. We constructed retroviral vectors carrying these cytokine genes under the control of the murine albumin enhancer and promoter and retrovirally transduced these genes into hepatoma and non-hepatoma cell lines. Strong expression of the cytokine genes was induced in transduced hepatoma cells, while no evident expression was detected in transduced non-hepatoma cells. These results demonstrate the hepatoma-specific expression of cytokine genes and imply the feasibility of in vivo gene transfer into hepatomas without affecting any other tissues. Furthermore, these cytokine genes were expressed much more intensively when they were derived from the albumin enhancer and promoter than when derived from the simian virus 40 early region promoter. These results indicate that transcriptional regulatory sequences specific for the target tissues could be preferable to viral promoters for the gene therapy of cancer.