Therapeutic oncolytic viruses: clinical advances and future directions.

PURPOSE OF REVIEW: The present review will highlight recent advances in the clinical application of oncolytic viral therapy. RECENT FINDINGS: Until recently, oncolytic viral researchers saw the immune system as an enemy that would clear the virus from the bloodstream. However, researchers now understand that sustained responses are seen in those patients with more robust antitumor immune responses. Much of the current focus in oncolytic viral research is trained on manipulation of the immune system to affect cancer cell killing in the tumor microenvironment and to facilitate durable systemic antitumor immunity. Many investigators have demonstrated synergistic effects of checkpoint inhibition and other immune therapies with viral administration. At the same time, insertion of various markers enables noninvasive deep tissue imaging. Finally, following regulatory approval in the United States and Europe, unbridled clinical use of T-VEC for patients with metastatic melanoma is also generating large volumes of patient data that will help elucidate strengths and weaknesses of oncolytic viral therapy. Perhaps the most telling sign of the field's future is a seismic shift in clinical trials with more investigators combining virus and immunotherapies. SUMMARY: This article reviews the current state of therapeutic oncolytic viruses in clinical use, and explores future directions of the field.