Journal
CANCER GENE THERAPY
Volume 27, Issue 3-4, Pages 246-255Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41417-019-0091-0
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Funding
- FOOD AND DRUG ADMINISTRATION [R01FD005379] Funding Source: NIH RePORTER
- NCATS NIH HHS [UL1 TR001417, UL1 TR003096] Funding Source: Medline
- NCI NIH HHS [P20 CA151129, R01 CA217179] Funding Source: Medline
- NIGMS NIH HHS [T32 GM063483] Funding Source: Medline
- FDA HHS [R01 FD005379] Funding Source: Medline
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Primary malignant central nervous system (CNS) tumors are the leading cause of childhood cancer-related death and morbidity. While advances in surgery, radiation, and chemotherapy have improved the survival rates in children with malignant brain tumors, mortality persists in certain subpopulations and current therapies are associated with extreme morbidity. This is especially true for children with malignant infratentorial tumors. Accordingly, G207, a genetically engineered herpes simplex virus (HSV-1) capable of selectively targeting cancer cells has emerged as a promising therapeutic option for this patient population. Herein, we demonstrate that cerebellar inoculation of G207 was systemically non-toxic in an immunocompetent, HSV-1 sensitive mouse strain (CBA/J). Mice had neither abnormal brain/organ pathology nor evidence of G207 replication by immunohistochemistry at days 7 and 30 after cerebellar G207 inoculation. While a minute amount viral DNA was recovered in the cerebellum and brainstem of mice at day 7, no viral DNA persisted at day 30. Critically, G207 delivered to the cerebellum was able to target/treat the highly aggressive MYC-overexpressed group 3 murine medulloblastoma increasing survival vs controls. These results provide critical safety and efficacy data to support the translation of G207 for pediatric clinical trials in intractable cerebellar malignancies.
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