Antiangiogenesis treatment for gliomas: Transfer of antisense vascular endothelial growth factor inhibits tumor growth in vivo

Presently, there is no effective treatment for glioblastoma, the most malig nant and common brain tumor. Angiogenic factors are potentially optimal tar gets for therapeutic strategies because they are essential for tumor growth and progression. In this study, we sought a strategy for efficiently deliv ering an antisense cDNA molecule of the vascular endothelial growth factor (VEGF) to glioma cells. The recombinant adenoviral vector Ad5CMV-alpha VEGF carried the coding sequence of wild-type VEGF(165) cDNA in an antisense or ientation, Infection of U-87 MG malignant glioma cells with the Ad5CMV-alph a VEGF resulted in reduction of the level of the endogenous VEGF mRNA and d rastically decreased the production of the targeted secretory form of the V EGF protein, Treatment of ss. human glioma tumors established in nude mice with intralesional injection of Ad5CMV-alpha VEGF inhibited tumor growth. T aken together, these findings indicate that the efficient down-regulation o f the VEGF produced by tumoral cells using antisense strategies has an anti tumor effect in vivo. This is the first time that an adenoviral vector is u sed to transfer antisense VEGF sequence into glioma cells in an animal mode l, and our results suggest that this system may have clinical and therapeut ic utility.