Oncolytic poliovirus against malignant glioma.

ABSTRACT

In cancerous cells, physiologically tight regulation of protein synthesis is lost, contributing to uncontrolled growth and proliferation. We describe a novel experimental cancer therapy approach based on genetically recombinant poliovirus that targets an intriguing aberration of translation control in malignancy. This strategy is based on the confluence of several factors enabling specific and efficacious cancer cell targeting. Poliovirus naturally targets the vast majority of ectodermal/neuroectodermal cancers expressing its cellular receptor. Evidence from glioblastoma patients suggests that the poliovirus receptor is ectopically upregulated on tumor cells and may be associated with stem cell-like cancer cell populations and proliferating tumor vasculature. We exploit poliovirus' reliance on an unorthodox mechanism of protein synthesis initiation to selectively drive viral translation, propagation and cytotoxicity in glioblastoma. PVSRIPO, a prototype nonpathogenic poliovirus recombinant, is scheduled to enter clinical investigation against glioblastoma.