• Gregory K Friedman, Joshua D Bernstock, Dongquan Chen, Li Nan, Blake P Moore, Virginia M Kelly, Samantha L Youngblood, Catherine P Langford, Xiaosi Han, Eric K Ring, Elizabeth A Beierle, G Yancey Gillespie, and James M Markert.
• Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, 35233, USA. gfriedman@peds.uab.edu.
• Sci Rep. 2018 Sep 17; 8 (1): 13930.

AbstractPediatric high-grade brain tumors and adult glioblastoma are associated with significant morbidity and mortality. Oncolytic herpes simplex virus-1 (oHSV) is a promising approach to target brain tumors; oHSV G207 and M032 (encodes human interleukin-12) are currently in phase I clinical trials in children with malignant supratentorial brain tumors and adults with glioblastoma, respectively. We sought to compare the sensitivity of patient-derived pediatric malignant brain tumor and adult glioblastoma xenografts to these clinically-relevant oHSV. In so doing we found that pediatric brain tumors were more sensitive to the viruses and expressed significantly more nectin-1 (CD111) than adult glioblastoma. Pediatric embryonal and glial tumors were 74-fold and 14-fold more sensitive to M002 and 16-fold and 6-fold more sensitive to G207 than adult glioblastoma, respectively. Of note, pediatric embryonal tumors were more sensitive than glial tumors. Differences in sensitivity may be due in part to nectin-1 expression, which predicted responses to the viruses. Treatment with oHSV resulted in prolonged survival in both pediatric and adult intracranial patient-dervied tumor xenograft models. Our results suggest that pediatric brain tumors are ideal targets for oHSV and that brain tumor expression of nectin-1 may be a useful biomarker to predict patient response to oHSV.

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