Abstract 2595: Vesicular stomatitis virus as a treatment for colorectal cancer

Abstract

Abstract Introduction: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. Despite progress in many aspects of combating colorectal cancer, the cause of death in nearly a third of all patients is metastatic disease. Vesicular stomatitis virus (VSV) is an attractive candidate as an oncolytic virus for the treatment of CRC due to its potent ability to induce apoptosis. Our group has generated a genetically engineered recombinant VSV containing an M protein mutation (rM51R) to enhance its tumor selectivity while preserving its oncolytic effects. As an extension of these findings, we hypothesized that oncolytic VSV can effectively treat CRC cells and therefore serve as an oncolytic therapy for the treatment of metastatic CRC. Methods: We compared the cytolytic effects of wild type (rwt) and M51R VSV in RKO, HCT116 and Lovo CRC cell lines via MTS assays. We initially sought to determine if CRC cells were susceptible to the oncolytic effects of VSV in single-cycle and multiple-cycle infection conditions. Viral protein synthesis and the production of viral progeny by CRC cell lines was quantified by S35 methionine labeling and viral plaque assays respectively. RKO tumor xenografts were established in athymic nude mice and injected with 108 pfu of M51R VSV. Results: We found that CRC cells display differential sensitivity to oncolytic VSV. RKO and HCT116 CRC cells were very sensitive to the oncolytic effects of both rwt and M51R viruses at 48 hours after both single and multiple-cycle infections. On the other hand, Lovo cells were somewhat resistant to VSV-induced cell killing under identical treatment conditions. All CRC cell lines supported the production of viral progeny with the peak viral production occurring at 36 hours after single and multiple-cycle infections with rwt and M51R VSV. Treatment of RKO xenografts with M51R VSV resulted in stabilization of tumor size relative to untreated controls after 21 days. Conclusions: These findings suggest that M51R VSV is a good candidate oncolytic virus for the treatment of metastatic colorectal cancer. Our future work will focus on defining the proportion of colorectal cancers that are susceptible to the oncolytic effects of VSV. In addition, we will identify molecular targets that may enhance the therapeutic efficacy of M51R VSV. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2595.