G207

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 Tlymphocyte (CTL) responses in addition to direct cytopathic effects. Derived from wild-type HSV-1 strain F, this agent has been neuroattenuated by deletionsin both copies of the gamma34.5 gene, the major determinant of HSVneurovirulence. 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 metabolismand viral DNA synthesis in nondividing cells but not individing cells.