Gene therapy for brain tumors: regression of experimental gliomas by adenovirus-mediated gene transfer in vivo.

TLDR

A replicative‑defective adenovirus carrying HSV‑tk was injected stereotactically into C6 glioma tumors in nude mice, followed by ganciclovir therapy to exploit the TK/GCV suicide system. The treatment reduced tumor cross‑sectional area 23‑fold and volume over 500‑fold, proving the adenoviral vector’s efficacy for glioma gene therapy.

Abstract

The therapeutic efficacy of adenovirus-mediated herpes simplex virus thymidine kinase (HSV-tk) gene transduction of rat C6 glioma cells followed by ganciclovir (GCV) administration was studied in tumors generated in the brains of nude mice. C6 glioma cells were efficiently transduced in vitro by a replicative-defective recombinant adenovirus carrying the HSV-tk gene (ADV/RSV-tk) that rendered them sensitive to GCV in a dose-dependent manner. Tumors were generated by stereotaxic intracerebral injection of 1 x 10(4) C6 cells in nude mice. After 8 days of tumor growth, 3 x 10(8) ADV/RSV-tk viral particles were injected into the tumors and the mice subsequently were treated with GCV for 6 days. Tumor size in untreated and treated animals was compared 20 days after tumor implantation. The mean cross-sectional area of the tumors in the treated animals was 23-fold smaller than in control animals and the tumor volume was reduced by > 500-fold. These results demonstrate that the recombinant adenoviral vector can function as an efficient gene delivery vehicle for the treatment of gliomas by in vivo gene therapy.