Effects of γ‐interferon gene‐modified hepatocytes on murine implanted liver carcinoma

Abstract

OBJECTIVE: Cancer immunotherapy and gene therapy are attractive approaches that have been widely investigated in different types of cancer. The present study examined the therapeutic effects of intrasplenically transplanted γ-interferon (IFN-γ) gene-modified hepatocytes on murine implanted liver carcinoma. METHODS: Embryonic murine hepatocytes (BNL.CL2) were transfected with a recombinant adenovirus encoding IFN-γ; two cell lines, BNL.LacZ and BNL.CL2, were used as controls. One week after intrasplenic C26 (colon carcinoma) cells were injected, 60 tumor-bearing syngeneic mice underwent the intrasplenic transplantation of IFN-γ gene-modified hepatocytes and were divided into treatment (BNL.IFN-γ) and control groups (BNL.LacZ and BNL.CL2). Two weeks later, the serum levels of IFN-γ, tumor necrosis factor-α (TNF-α) and nitric oxide (NO) in the implanted liver carcinoma-bearing mice were assayed, the cytotoxicity of splenic cytotoxic T lymphocytes (CTL) were measured, and the mor-phology of the hepatic tumors was studied to evaluate the therapeutic effects of the treatment. RESULTS: In the treatment group, the serum levels of IFN-γ, TNF-α and NO increased significantly (P < 0.01), and the splenic CTL activity also increased markedly (P < 0.01), accompanied by a substantial decrease in tumor volume and an increase in survival. CONCLUSIONS: These data indicate that the IFN-γ recombinant adenovirus was able to exert potent therapeutic effects and that the intrasplenic transplantation of adenovirus-mediated IFN-γ gene- modified hepatocytes could be used as a treatment for implanted liver carcinoma.