Treatment of experimental glioma by administration of adenoviral vectors expressing Fas ligand

Fas ligand (FasL) is a cytokine, produced by activated T cells and NK cells , that triggers apoptosis of Fas-positive target cells including human glio ma cells. As shown here, in vitro infection of rat F98 and human LN18 gliom a cell lines with recombinant adenovirus (rAd) expressing Fast cDNA under c ontrol of the cytomegalovirus promoter (rAd-CMV-FasL) induced striking cyto toxicity in Fas-positive glioma cell lines but not in the Fas-negative F98 glioma subline F98/ZH. The extent of Fast-mediated cytotoxic effects outran ged the expectations based on expression of beta-galactosidase (beta-Gal) b y F98 cells infected with a control virus expressing the lacZ gene (rAd-CMV -lacZ), The detection of FasL bioactivity in supernatants of infected cells provides evidence of a bystander mechanism involving the cytotoxic action of Fast on uninfected cells. In F98 tumor-bearing rats, infection with rAd- CMV-FasL increased the mean survival time by 50% compared with infection wi th rAd-CMV-lacZ or untreated controls. These data suggest that viral vector transduction of the Fast gene could be part of a successful glioma gene th erapy.