Oncolytic virotherapy for pediatric malignancies: future prospects

Alicia M Waters,1 Gregory K Friedman,2 Eric K Ring,2 Elizabeth A Beierle1 1Department of Surgery, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; 2Department of Pediatrics, Division of Hematology-Oncology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA Abstract: Pediatric solid tumors remain a major health concern, with nearly 16,000 children diagnosed each year. Of those, ~2,000 succumb to their disease, and survivors often suffer from lifelong disability secondary to toxic effects of current treatments. Countless multimodality ­treatment regimens are being explored to make advances against this deadly disease. One targeted treatment approach is oncolytic virotherapy. Conditionally replicating viruses can infect tumor cells while leaving normal cells unharmed. Four viruses have been advanced to pediatric clinical trials, including herpes simplex virus-1, Seneca Valley virus, reovirus, and vaccinia virus. In this review, we discuss the mechanism of action of each virus, pediatric preclinical studies conducted to date, past and ongoing pediatric clinical trials, and potential future direction for these novel viral therapeutics. Keywords: oncolytic virus, herpes simplex virus, Seneca Valley virus, reovirus, vaccinia