Antivascular activity of VB111 in glioblastoma xenografts.

Abstract

e13652 Background: 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 (VDA) for cancer treatment. VB-111 is aimed to specifically destroy existing angiogenic blood vessels in a potentially 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 c transgene. We hypothesized that VB-111 would have significant activity in glioblastoma. Methods: Intracranial xenografts were established in nude rats with a luciferase expressing U87 glioma cell line. Rats were treated intravenously with a single dose of 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: Rats bearing U87 tumors treated with a single dose of VB-111 showed a significant prolongation of median survival (39.25 days control vs. 45.8 days VB- 111), decreased median luciferase activity at all time points post treatment, and decreased median tumor size on MRI at all time points post treatment. Conclusions: Anti-angiogenic therapy with VB-111 appears to be promising for glioblastoma. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Vascular Biogenics Vacular Biogenics