Myeloid derived suppressor cells as a vehicle for tumor-specific oncolytic viral therapy

One of the several impediments to effective oncolytic virus therapy of cancer remains a lack of tumor-specific targeting. Myeloid derived suppressor cells (MDSCs) are immature myeloid cells induced by tumor factors in tumor-bearing hosts. The biodistribution kinetics of MDSC and other immune cell types in a murine hepatic colon cancer model was investigated through the use of tracking markers and magnetic resonance imaging (MRI). MDSCs were superior to other immune cell types in preferential migration to tumors in comparison to other tissues. Based on this observation, we engineered a strain of vesicular stomatitis virus (VSV), an oncolytic rhabdovirus, that bound MDSCs and used them as a delivery vehicle. Improving VSV binding efficiency to MDSCs extended the long-term survival of mice bearing metastatic colon tumors, compared to systemic administration of wild-type VSV alone. Survival was further extended by multiple injections of the engineered virus without significant toxicity. Notably, direct tumor killing was accentuated by promoting MDSC differentiation towards the classically activated M1-like phenotype. Our results offer a preclinical proof of concept for using MDSCs to facilitate and enhance the tumor-killing activity of tumor-targeted oncolytic therapeutics.