MB-41: INTRAVENTRICULAR ONCOLYTIC ENGINEERED HERPES SIMPLEX VIRUS PROLONGS SURVIVAL AND REDUCES SPINAL METASTASES IN MICE BEARING HUMAN GROUP 3 MEDULLOBLASTOMA

Outcomes are especially poor for children with group 3 medulloblastoma, and surviving patients often suffer from lifelong neurocognitive, psychosocial, and neuroendocrine impairments secondary to current therapies including surgery, chemotherapy and radiation. Oncolytic herpes simplex virus (oHSV) is a novel, promising approach for targeting pediatric medulloblastoma. Through engineered mutations (e.g. γ₁34.5 neurovirulence gene deletions), oHSV replicates in and kills cancer cells while sparing normal cells. Our group and others have successfully utilized intratumoral inoculation of the virus; however this route of delivery does not directly target metastatic spinal disease frequently seen in medulloblastoma. We hypothesized that intraventricular oHSV could target metastatic medulloblastoma. Athymic nude mice were injected intraventricularly with 5x10⁵ bioluminescently-enabled D341MED group 3 human medulloblastoma cells expressing luciferase. Five days later, 10 mice received 10 microliters of intraventricular 10% glycerol in saline or 1x10⁶ plaque forming units (pfu) of G207, a γ₁34.5-deleted oHSV that is currently being used intratumorally in a phase I study in children with recurrent or progressive supratentorial brain tumors (clinicaltrials.gov NCT02457845). Bioluminescent imaging was performed weekly, and counts/second was measured in the neuraxis. Mice that developed neurologic morbidity were euthanized and survival times were measured. Median survival times were significantly increased from 12.0 ± 0.5 to 18.0 ± 0.9 days with a single G207 treatment (p = 0.008). Metastases quantified by bioluminescence were significantly decreased (p = 0.02) one week after G207 treatment. These data indicate that intraventicular oHSV can successfully target metastatic pediatric medulloblastoma in mice. Further studies examining the safety and efficacy of intraventricular oHSV are in progress