Although
xenotransplantation of retrovirus-producing cells into a
tumor has been shown to be effective for the treatment of
cancer,
injections of recombinant retroviruses are much more feasible for clinical applications. We established a clone producing retroviruses carrying the herpes simplex virus
thymidine kinase (HSVtk) gene with titers of up to 4 x 10(7) colony-forming units/ml, and examined the effectiveness of in vivo gene therapy against
cancer. Syngeneic mice were inoculated subcutaneously with murine
hepatocellular carcinoma (HCC) cells, BNL1ME A.7R.1, and the treatment was initiated after
tumors were established. When mice were given an intratumoral injection of HSVtk-carrying retroviruses or their producing cells followed by
ganciclovir (GCV) treatment, significantly prolonged survival periods were observed. When mice were treated with repeated intratumoral
injections of HSVtk-carrying retrovirus-producing cells, significant antitumor responses and some cures were induced by GCV treatment. Furthermore, repeated intratumoral
injections of HSVtk-carrying retroviruses and GCV treatment resulted in complete regression of established HCC
tumors in all animals used in the experiment. Mice that completely eradicated
tumors exhibited protective immunity against wild-type HCC
tumors. These results suggest that repeated
injections of HSVtk-carrying retroviruses followed by GCV treatment is a potent modality for the treatment of solid
tumors.