Combined effects of radiotherapy and angiostatin gene therapy in glioma tumor model

The objective of the present study was to evaluate the antitumor effect of a defective adenovirus expressing a secretable angiostatin-like molecule (A dK3) in combination with radiotherapy in rat C6 gliomas s.c. preestablished into athymic mice. In vitro, the combination regimen was significantly (P < 0.001) more cytotoxic for human microcapillary endothelial cells than eit her treatment alone, whereas survival of C6 glioma cells was not affected i n the conditions used. Radiotherapy and AdK3 gene delivery was then studied on well established C6 xenografts (165 +/- 70 mm(3)). In these tumors, AdK 3 intratumoral injections had only a marginal effect. Interestingly, when e xperimental radiotherapy was added, significantly higher (P < 0.005), and p ossibly synergistic, antitumoral effects were observed that tightly correla ted a marked decrease of intratumoral vascularization. The combination of r adiotherapy and AdK3 intratumoral injections also revealed a significant (P < 0.05) inhibition of tumor growth as compared with either treatment alone for larger tumors (467 +/- 120 mm(3)). Altogether, these data emphasize th e potential of combining a destructive strategy directed against the tumor cells with an anti-angiogenic approach to fight cancer.