Mechanism of action
From the NCI Drug Dictionary: A neuroattenuated, replication-competent, recombinant herpes simplex virus-1 (HSV-1) with potential oncolytic activity. Upon intracerebral administration, oncolytic HSV-1 G207 preferentially replicates within glioma cells, which may elicit tumor-specific systemic immune and cytotoxic T lymphocyte (CTL) responses in addition to direct cytopathic effects. Derived from wild-type HSV-1 strain F, this agent has been neuroattenuated by deletions in both copies of the gamma34.5 gene, the major determinant of HSV neurovirulence. In addition, the HSV-1 gene UL39, encoding the viral ribonucleotide reductase large subunit infected cell protein 6 (ICP6), has been inactivated through the insertion of the Escherichia coli lacZ gene. By inactivating UL39, viral ribonucleotide reductase activity is disrupted, resulting in the inhibition of nucleotide metabolism and viral DNA synthesis in nondividing cells but not in dividing cells.
- UAB 1472: Friedman GK, Johnston JM, Bag AK, Bernstock JD, Li R, Aban I, Kachurak K, Nan L, Kang KD, Totsch S, Schlappi C, Martin AM, Pastakia D, McNall-Knapp R, Farouk Sait S, Khakoo Y, Karajannis MA, Woodling K, Palmer JD, Osorio DS, Leonard J, Abdelbaki MS, Madan-Swain A, Atkinson TP, Whitley RJ, Fiveash JB, Markert JM, Gillespie GY. Oncolytic HSV-1 G207 Immunovirotherapy for Pediatric High-Grade Gliomas. N Engl J Med. 2021 Apr 29;384(17):1613-1622. Epub 2021 Apr 10. link to original article PubMed NCT02457845