Zika virus as an oncolytic therapy

Abstract

Glioblastoma (GBM) is a common, aggressive, primary brain tumor. New therapies are needed to improve outcomes in patients with this disease. One such approach which has shown preclinical promise is the use of genetically engineered Zika virus for oncolytic virotherapy. Zika virus is an enveloped, positive-sense, single-stranded RNA virus and is spread by mosquitoes of the Aedes genus. Most infections with Zika virus in adults are asymptomatic. However, primary infection with Zika virus early during pregnancy can cause fetal congenital defects. This phenomenon, termed congenital Zika syndrome, is thought to be the result of infection of fetal neural stem cells. The development of Zika virus as an oncolytic for GBM arose from the discovery that Zika virus infects and kills GBM stem cells. GBM stem cells have similarities to fetal neural stem cells and are a subpopulation of cells within the tumor that are refractory to treatment and likely drive tumor persistence and re-occurrence. In preclinical models of GBM, infection with Zika virus triggers immune-mediated clearance of orthotopically transplanted tumors and leads to development of immunological memory. The propensity of Zika virus to infect GBM stem cells along with limited systemic toxicities and transmissibility make Zika virus an ideal candidate for development as an oncolytic therapy.

Keywords: Glioblastoma; Neuroblastoma; Oncolytic virotherapy; Zika virus; Zikv-3′utr-∆10-lav.