Oncolytic virus therapy of multiple tumors in the brain requires suppression of innate and elicited antiviral responses

The occurrence of multiple tumors in an organ heralds a rapidly fatal cours e. Although intravascular administration may deliver oncolytic viruses/vect ors to each of these tumors, its efficiency is impeded by an antiviral acti vity present in complement-depleted plasma of rodents and humans. Here, thi s activity was shown to interact with complement in a calcium-dependent fas hion, and antibody neutralization studies indicated preimmune IgM has a con tributing role. Short-term exposure to cyclophosphamide (CPA) partially sup pressed this activity in rodents and humans. At longer time points, cycloph osphamide also abrogated neutralizing antibody responses. Cyclophosphamide treatment of rats with large single or multiple intracerebral tumors substa ntially increased viral survival and propagation, leading to neoplastic reg ression.