Zika Virus Treatment Prolongs Survival in Mice Bearing Patient Derived Glioblastoma Tumors

Introduction: Zika virus (ZIKV) is an RNA virus in the Flaviviridae family. It is an ideal oncolytic virus candidate for the treatment of glioblastoma (GBM) as it is neurotropic (crosses the blood brain barrier), agnostic to the intra- and inter-tumoral heterogeneity of GBM and can transform the immunoinhibitory GBM microenvironment to an immunostimulatory one. In this study, we investigated the oncolytic efficacy of two naturally occurring ZIKV strains in a GBM patient derived xenograft (PDX) model.

Methods: Intracerebral GBM tumors were stereotactically established in immunocompromised mice. Tumor size was determined by bioluminescence imaging (BLI). Mice with tumors of similar size were randomized to the control, ZIKV1, or ZIKV2 treatment. Treatment was delivered either intratumorally or intravenously. Mice were followed clinically and with BLI.

Results: For intratumoral treatment, there were 21 mice in the control treatment group, and 22 mice in both the ZIKV1 and ZIKV2 treatment groups. At 120 days, the median survival was 21 days in the control group, 63 days in the ZIKV1 group, and not reached in the ZIKV2 group. Amongst the 15 complete responders in the ZIKV1 group, 6 succumbed to weight loss whereas no mouse in the ZIKV2 group experienced weight loss. For mice treated intravenously, at 90 days, the median survival of the control group (N=10) was 21 days, while the median survival in the ZIKV2 group (N=8) was again not reached. In an intratumoral dose escalation trial, 8 of 10 mice treated with as few as 100 plaque forming units of ZIKV2 were thriving at 90 days.

Conclusion : We conclude that the naturally occurring ZIKV1 and ZIKV2 strains have remarkable anti-GBM efficacy in our PDX model. No ZIKV2 treated mouse experienced weight loss. Therefore, additional investigation of ZIKV2 as a novel treatment for GBM is warranted.