Abstract
Malignant gliomas, the most lethal type of primary brain tumor, continue to be a major therapeutic challenge. Here, we found that enterovirus A71 (EV-A71) can be developed as a novel oncolytic agent against malignant gliomas. EV-A71 preferentially infected and killed malignant glioma cells relative to normal glial cells. The virus receptor human scavenger receptor class B, member 2 (SCARB2), and phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1)-mediated cell death were involved in EV-A71-induced oncolysis. In mice with implanted subcutaneous gliomas, intraneoplastic inoculation of EV-A71 caused significant tumor growth inhibition. Furthermore, in mice bearing intracranial orthotopic gliomas, intraneoplastic inoculation of EV-A71 substantially prolonged survival. By insertion of brain-specific microRNA-124 (miR124) response elements into the viral genome, we improved the tumor specificity of EV-A71 oncolytic therapy by reducing its neurotoxicity while maintaining its replication potential and oncolytic capacity in gliomas. Our study reveals that EV-A71 is a potent oncolytic agent against malignant gliomas and may have a role in treating this tumor in the clinical setting.