Adenovirus-mediated gene therapy of experimental glioma in the rat

Our aim was to test the therapeutic effects of adenovirus-mediated gene therapy in an animal model of brain tumor which was obtained by injection of 9L gliosarcoma cells into the caudate nucleus of rat brains. Seven days after the implantation of tumor cells, adenovirus vectors bearing the Escherichia coli beta galactosidase gene (ADV beta-gal) or the herpes simplex virus thymidine kinase gene (ADVtk) were stereotactically injected in the tumor. Injection of the ADV beta gal resulted in the expression of the marker gene in 61% of the animals. Transfer of the ADVtk was followed, 3 days later, by intraperitoneal injection of ganciclovir (GCV) for 10 days. A control group was treated with saline instead of GCV. We observed a significant regression of the tumors in 50% of the rats treated with ADVtk and GCV as compared with control animals. In 4 cases out of 6, the tumor completely disappeared after treatment. These results demonstrate the potentiel efficacy of adenovirus-mediated transfer of the HSVtk gene following by GCV administration of the treatment of glioblastomas.