Viral shedding and biodistribution of G207, a multimutated, conditionally replicating herpes simplex virus type 1, after intracerebral inoculation inAotus

G207 is a multimutated, conditionally replicating herpes simplex virus type 1 (HSV-1) that is currently in clinical trial for patients with malignant glioma. G207 exhibits an efficient oncolytic activity in tumor cells, yet m inimal toxicity in normal tissue when injected into the brains of HSV-susce ptible mice or nonhuman primates. In this study, we evaluated the shedding and biodistribution of clinical-grade G207 after intracerebral inoculation (3 x 10(7) pfu) in four New World owl monkeys (Aotus nancymae). Using PCR a nalyses and viral cultures, neither infectious virus nor viral DNA was dete cted from tear, saliva, or vaginal secretion samples at any time point up t o 1 month postinoculation. Analyses of tissues obtained at necropsy at 1 mo nth from two of the four monkeys, plus one monkey inoculated with laborator y-grade G207 (10(9) pfu) 2 years earlier, showed the distribution of G207 D NA restricted to the brain, although infectious virus was not isolated. His topathology revealed normal brain tissues including the sites of inoculatio n. A measurable increase of serum anti-HSV antibody titer was observed in a ll monkeys, as early as 21 days postinoculation. The results ascertain the safety of G207 in the brain and indicate that strict biohazard management m ay not be required for G2O7-treated patients.