Oncolytic Hsv (34.5enve) Sensitizes Bortezomib-Induced Cancer Cell Killing Through Induction Of Rip1 Dependent Necroptosis

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC The aim of this study is to evaluate the combination of oncolytic herpes simplex virus (34.5ENVE) and bortezomib in the treatment of solid tumors. Although phase 1 clinical trials of oncolytic viruses have established the relative safety of this approach, evidence for efficacy has remained elusive. Therefore, strategies to enhance the efficacy of this treatment are being explored. We investigated the impact of 34.5ENVE in combination with bortezomib, a potent and selective proteosome inhibitor, in the treatment of multiple solid tumor models. In vitro, various human cancer cells were treated with bortezomib alone, 34.5ENVE alone, or the combination of the two. We analyzed the treatments for synergism in cancer cell killing using Chou-Talalay analysis (CI index 0.8). These findings suggest that the combination of bortezomib and 34.5ENVE leads to synergistic cell killing mediated by RIP1 dependent necroptosis induction. Citation Format: Brian S. Hurwitz, Ji Young Yoo, Chelsea Bolyard, Jun-Ge Yu, Jeffery Wojton, Matthew Old, Balveen Kaur. Oncolytic HSV (34.5ENVE) sensitizes bortezomib-induced cancer cell killing through induction of RIP1 dependent necroptosis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3312. doi:10.1158/1538-7445.AM2013-3312