Mesenchymal stromal cells protect combined oncolytic and helper-dependent adenoviruses from humoral immunity.

Systemic delivery of oncolytic and immunomodulatory adenoviruses may be required for optimal effects on human malignancies. Mesenchymal stromal cells (MSCs) can serve as delivery systems for cancer therapeutics due to their ability to transport and shield these agents while homing to tumors. We now use MSCs to deliver a clinically validated binary oncolytic and helper-dependent adenovirus combination (CAdVEC) to tumor cells. We show successful oncolysis and helper-dependent virus function in tumor cells even in the presence of plasma from adenovirus-seropositive donors. In both two- and three-dimensional cultures, CAdVEC function is eliminated even at high dilutions of seropositive plasma but is well sustained when CAdVEC is delivered by MSCs. These results provide a robust in vitro model to measure oncolytic and helper-dependent virus spread and demonstrate a beneficial role of using MSCs for systemic delivery of CAdVEC even in the presence of a neutralizing humoral response.