Abstract 5400: Antiangiogenic gene therapy with VB111 is active in glioblastoma xenografts

Introduction: Glioblastoma is a highly vascular tumor with marked endothelial dependence. While anti-angiogenic therapy has shown transient clinical benefit for the treatment of glioblastoma, persistent vascularization is seen with a normalization of blood vessels within the tumor. VB-111 is a dual-action, anti-angiogenic and vascular disrupting agent for cancer treatment aimed specifically at destroying newly formed and existing tumor blood vessels in a safe and efficient manner. VB-111 consists of a replication incompetent adenovirus together with an endothelial angiogenic-specific promoter and a pro-apoptotic Fas chimera transgene. Methods: Intracranial xenografts were established in nude rats with a luciferase expressing U87 glioma cell line. Rats were treated intravenously with VB-111 at 1011 viral particles or placebo at 21 days post tumor cell implantation. Tumor growth was followed by in vivo bioluminescent imaging and 7T MRI. Rats were sacrificed when moribund or when marked neurologic deficit was observed. Tumors were evaluated by standard histologic methods for vessel density and necrosis. Results: Untreated rats bearing U87 tumors showed a median survival of 38 days (95% CI 35.1-40.9 days), while animals treated with VB-111 showed a median survival of 48 days (95% CI 42.1-53.9 days). Log rank analysis of survival distributions between these two groups showed a significant difference (p=0.024) in favor of treatment. Luciferase activity, used as a surrogate for tumor volume, began separating between the two groups in week two post treatment and showed a continued trend for reduced activity in the treatment group thereafter. MRI imaging confirmed decreased tumor size in representative animals from the VB-111 group. Conclusions: VB-111's Dual action therapy is promising for glioblastoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5400. doi:10.1158/1538-7445.AM2011-5400