COMBINATION GENE-THERAPY FOR LIVER METASTASIS OF COLON-CARCINOMA IN-VIVO

The efficacy of combination therapy with a ''suicide gene'' and a cyto kine gene to treat metastatic colon carcinoma in the liver was investi gated. Tumor in the liver was generated by intrahepatic injection of a colon carcinoma cell line (MCA-26) in syngeneic BALB/c mice. Recombin ant adenoviral vectors containing various control and therapeutic gene s were injected directly into the solid tumors, followed by treatment with ganciclovir. While the tumors continued to grow in all animals tr eated with a control vector or a mouse interleukin 2 vector, those tre ated with a herpes simplex virus thymidine kinase vector, with or with out the coadministration of the mouse interleukin 2 vector, exhibited dramatic necrosis and regression. However, only animals treated with b oth vectors developed an effective systemic antitumoral immunity again st challenges of tumorigenic doses of parental tumor cells inoculated at distant sites. The antitumoral immunity was associated with the pre sence of MCA-26 tumor-specific cytolytic CD8(+) T lymphocytes. The res ults suggest that combination suicide and cytokine gene therapy in viv o can be a powerful approach for treatment of metastatic colon carcino ma in the liver.