1. ^*Molecular Neurosurgery Laboratory, Department of Neurosurgery, Georgetown University Medical Center, Washington, District of Columbia, 20007
2. ^†Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, Washington, District of Columbia, 20007
3. ^§Division of Comparative Medicine, Georgetown University Medical Center, Washington, Washington, District of Columbia, 20007
4. ^‡Clinical Virology Laboraty, University of Alabama at Birmingham, Birmingham, Alabama, 35294
5. ^¶NeuroVir Therapeutics Incorporated, San Diego, California, 92121

Correspondence: Tomoki Todo, Molecular Neurosurgery Laboratory, Massachusetts General Hospital-East, 149, 13th Street, Box 17, Charlestown, MA 02129. Fax: (617)724-9610. E-mail: todo@helix.mgh.harvard.edu.

¹Current address: Midwest Neurosurgery Associates, 6420 Prospect, Kansas City, MO 64132.

²Current address: Massachusetts General Hospital-East, 149, 13th Street, Box 17, Charlestown, MA 02129.

³Current address: Division of Lab Animal Resources, S1050BST, 3500 Terrace Street, University of Pittsburgh, Pittsburgh, PA 15261.

⁴Current address; Department of Anatomy & Cell Biology, Room 416, Medical Sciences Building, University of Western Ontario, London, Ontario N6A 5C1, Canada.

⁵Current address: Massachusetts General Hospital, 55 Fruit Street, WHT 502, Boston, MA 02114.

Received 2 August 2000; Accepted 3 October 2000.

Abstract

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 minimal toxicity in normal tissue when injected into the brains of HSV-susceptible mice or nonhuman primates. In this study, we evaluated the shedding and biodistribution of clinical-grade G207 after intracerebral inoculation (3 10⁷ pfu) in four New World owl monkeys (Aotus nancymae). Using PCR analyses and viral cultures, neither infectious virus nor viral DNA was detected from tear, saliva, or vaginal secretion samples at any time point up to 1 month postinoculation. Analyses of tissues obtained at necropsy at 1 month from two of the four monkeys, plus one monkey inoculated with laboratory-grade G207 (10⁹ pfu) 2 years earlier, showed the distribution of G207 DNA restricted to the brain, although infectious virus was not isolated. Histopathology revealed normal brain tissues including the sites of inoculation. A measurable increase of serum anti-HSV antibody titer was observed in all monkeys, as early as 21 days postinoculation. The results ascertain the safety of G207 in the brain and indicate that strict biohazard management may not be required for G207-treated patients.