Adenovirus‐mediated gene therapy of experimental gliomas

摘要: The efficacy of adenovirus (ADV)-mediated gene therapy to treat brain tumors was tested in a syngeneic glioma model. Tumor cells were transduced situ with replication-defective ADV carrying the herpes simplex virus thymidine kinase (HSV-tk) controlled by Rous sarcoma promoter. Expression HSV-tk enables cell convert drug ganciclovir form that is cytotoxic dividing cells. Tumors generated Fischer 344 rats stereotaxic implantation 9L gliosarcoma into caudate nucleus. Eight days later, injected either (ADV-tk) or control vector containing β-galactosidase (ADV-βgal) and treated saline. size measured 20 after at death. Rats ADV-βgal ADV-tk saline had large tumors. No detected animals doses ≥80mg/kg. An infiltrate macrophages lymphocytes injection site indicated an active local immune reaction. In survival studies, all have remained alive longer than 80 up 120 tumor induction whereas untreated died 22 days. These results demonstrate ADV-mediated transfer vivo confers sensitivity ganciclovir, represents potential method treatment © 1994 Wiley-Liss, Inc.