Designing and building oncolytic viruses

Maroun, Justin; Muñoz-Alía, Miguel; Ammayappan, Arun; Schulze, Autumn; Peng, Kah-Whye; Russell, Stephen

OV therapy begins with the administration of the virus to the patient just as with any other drug. Several approaches can be taken, each with to optimize oncolytic virotherapy indicated that maximizing delivery, so more tumor cells are infected, has a profound impact on the degree to which the virus must propagate from each infected cell for curative therapy [60] . The higher the number and the more random the dispersion of infectious centers established in a tumor after delivery of virus, the more effective the virus will be, although these parameters must be optimized for each virus and model [61] . IV and IT administrations of OVs are common delivery methods that introduce large amounts of virus into one compartment in a very short time. This rapid delivery of a massive virus inoculum does not parallel what typically occurs in a natural infection and potentially allows the IT spread of the OV infection to outpace host defenses. Successful delivery in the context of an OV infection requires that a critical viral concentration is achieved within the tumor to allow for sufficient oncolysis and systemic spread of the virus to all sites of disease in a safe and reproducible pattern.