Enhancement of Vaccinia Virus Based Oncolysis with Histone Deacetylase Inhibitors

Abstract

Histone deacetylase inhibitors (HDI) dampen cellular immune response by decreasing interferon production and have been shown to increase the replication of Vesicular Stomatitis Virus and HSV. As attenuated tumour-selective oncolytic vaccinia viruses (VV) are already undergoing clinical evaluation, the goal of this study is to determine whether HDI can also enhance the potency of these poxviruses in infection-resistant cancer cell lines. Multiple HDIs were tested and Trichostatin A (TSA) was found to potently enhance the spread and replication of a tumour selective VV in several infection-resistant cancer cell lines. TSA significantly decreased the number of lung metastases in a syngeneic B16F10LacZ lung metastasis model yet TSA treatment did not increase the replication of VV in normal tissues. We conclude that TSA can selectively and effectively enhance the replication and spread of oncolytic vaccinia virus in cancer cells.