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Safety and efficacy of oncolytic HSV-1 G207 inoculated into the cerebellum of mice.
- Source :
-
Cancer gene therapy [Cancer Gene Ther] 2020 Apr; Vol. 27 (3-4), pp. 246-255. Date of Electronic Publication: 2019 Mar 28. - Publication Year :
- 2020
-
Abstract
- 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.
- Subjects :
- Animals
Brain Stem pathology
Brain Stem virology
Cell Line, Tumor transplantation
Cerebellar Neoplasms immunology
Cerebellar Neoplasms pathology
Cerebellum pathology
Cerebellum virology
DNA, Viral isolation & purification
Disease Models, Animal
Genetic Engineering
Herpesvirus 1, Human genetics
Humans
Injections, Intralesional
Medulloblastoma immunology
Medulloblastoma pathology
Mice
Mice, Inbred CBA
Oncolytic Virotherapy adverse effects
Oncolytic Viruses genetics
Oncolytic Viruses immunology
Cerebellar Neoplasms therapy
Herpesvirus 1, Human immunology
Medulloblastoma therapy
Oncolytic Virotherapy methods
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5500
- Volume :
- 27
- Issue :
- 3-4
- Database :
- MEDLINE
- Journal :
- Cancer gene therapy
- Publication Type :
- Academic Journal
- Accession number :
- 30918335
- Full Text :
- https://doi.org/10.1038/s41417-019-0091-0