HERPES-SIMPLEX VIRUS THYMIDINE KINASE GENE-THERAPY FOR RAT MALIGNANT BRAIN-TUMORS

Transfer of a herpes simplex virus-derived thymidine kinase (HSV-tk) g ene into brain tumor cells and subsequent ganciclovir (GCV) treatment has been shown by others to be an effective treatment in rats with int racerebrally inoculated 9L gliosarcomas. Mechanism of action and repro ducibility are, however, still a matter of debate. We have used the sa me model to test the therapeutic effects of both retrovirus- and adeno virus-mediated transfer of the HSV-tk gene followed by GCV treatment. Survival time of rats with intracerebral 9L tumors was significantly p rolonged after a single administration of adenovirus carrying a HSV-tk gene as compared to controls. Retrovirus-mediated gene transfer also resulted in significantly prolonged survival time when recombinant ret rovirus-producing cells were transplanted. Direct injection of the rec ombinant retrovirus, HSV-tk-expressing cells, virus-producing cells wi thout GCV administration and recombinant retrovirus-lacZ or interleuki n-2 (IL-2)-producing cells did nor result in tumor cell kill. In the p resent study, no significant difference in survival of 9L brain tumor carrying rats was found after treatment with adenovirus as compared to retrovirus-mediated HSV-tk-mediated gene transfer and subsequent GCV treatment.