ABSTRACT
Poliovirus has recently been added to the rapidly expanding list of potential viral oncolytic agents. Its inherent tropism for certain malignant cell types, highly lytic growth cycle, and
permissiveness for genetic manipulation qualify poliovirus as a prime target for therapeutic use against cancer. On the other hand, the danger of serious neurological damage following administration of poliovirus-based oncolytic agents restricts its use. We have developed an innovative strategy to harness poliovirus for therapeutic use against central nervous system (CNS) malignancy. Our approach is the result of thorough analyses of the molecular pathogenesis of poliomyelitis and takes advantage of the natural targeting and invasive properties of poliovirus. We have exploited an unconventional mechanism of translation initiation upon which poliovirus relies to achieve a tumor-specific replication phenotype and to exclude viral cytopathogenicity in normal tissues.
