Despite intensive research efforts and therapeutic advances over the last few decades, the pediatric
neural crest tumor,
neuroblastoma, continues to be responsible for over 15% of pediatric
cancer deaths. Novel therapeutic options are needed for this
tumor. Recently, investigators have shown that mice with syngeneic murine
gliomas treated with an engineered, neuroattenuated oncolytic
herpes simplex virus-1 (oHSV), M002, had a significant increase in survival. M002 has deletions in both copies of the γ 1 34.5 gene, enabling replication in
tumor cells but precluding
infection of normal neural cells. We hypothesized that M002 would also be effective in the
neural crest tumor,
neuroblastoma. We showed that M002 infected, replicated, and decreased survival in
neuroblastoma cell lines. In addition, we showed that in murine xenografts, treatment with M002 significantly decreased
tumor growth, and that this effect was augmented with the addition of ionizing radiation. Importantly, survival could be increased by subsequent doses of radiation without re-dosing of the virus. Finally, these studies showed that the primary entry
protein for oHSV, CD111 was expressed by numerous
neuroblastoma cell lines and was also present in human
neuroblastoma specimens. We concluded that M002 effectively targeted
neuroblastoma and that this oHSV may have potential for use in children with unresponsive or relapsed
neuroblastoma.