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Ref Type | Journal Article | ||||||||||||
PMID | (30918335) | ||||||||||||
Authors | Bernstock JD, Vicario N, Li R, Nan L, Totsch SK, Schlappi C, Gessler F, Han X, Parenti R, Beierle EA, Whitley RJ, Aban I, Gillespie GY, Markert JM, Friedman GK | ||||||||||||
Title | Safety and efficacy of oncolytic HSV-1 G207 inoculated into the cerebellum of mice. | ||||||||||||
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Abstract Text | 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. |
Molecular Profile | Treatment Approach |
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Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
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Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
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HSV-1 G207 | HSV-1 G207 | 0 | 2 |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
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HSV-1 G207 | G207|Oncolytic HSV-1 G207|HSV-1-G207|HSV-1G207 | HSV-1 G207 is an oncolytic herpes simplex virus-1 (HSV-1), which may lead to antitumor activity, including cytotoxicity and inhibition of angiogenesis and tumor growth (PMID: 15720798, PMID: 30918335). |
Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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