Induction of therapeutic antitumor antiangiogenesis by intratumoral injection of genetically engineered endostatin-producing Semliki Forest virus

Antiangiogenic therapy using Semliki Forest virus (SFV) carrying Endostatin gene for malignant brain tumor was investigated to improve the therapeutic efficacy. The efficiency of SFV-mediated gene delivery was first evaluated for B 16 cells and compared with the efficiency in cells of endothelial or igin (HMVECs). HMVECs are more susceptible to SFV infection than B 16 cells . For the in vivo treatment model, phosphate-buffered saline, SFV-LacZ, ret rovirus vector GCsap-Endostatin, and SFV-Endostatin were injected to mice b earing B 16 brain tumors. A very significant inhibition of tumor growth was observed in the group that had been treated with SFV-Endostatin. A marked reduction of intratumoral vascularization was seen in the tumor sections fr om the SFV-Endostatin group compared with tumor sections from the SFV-LacZ or GCsap-Endostatin groups. Moreover, at day 7 after intravenous administra tion of SFV-Endostatin, the serum level of endostatin was augmented more th an 3-fold compared to that after intravenous administration of GCsap-Endost atin. The results indicated that treatment with SFV-Endostatin inhibited th e angiogenesis with established tumors. Gene therapy with Endostatin delive red via SFV may be a candidate for the development of new therapy for brain tumors.