Viral shedding and biodistribution of G207, a multimutated, conditionally replicating herpes simplex virus type 1, after intracerebral inoculation in aotus.
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 x 10(7) 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 (10(9) 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.
Todo
T
T
Molecular Neurosurgery Laboratory, Massachusetts General Hospital-East,Charlestow, District of Columbia, 20007, USA. todo@helix.mgh.harvard.edu
Feigenbaum
F
F
Rabkin
S D
SD
Lakeman
F
F
Newsome
J T
JT
Johnson
P A
PA
Mitchell
E
E
Belliveau
D
D
Ostrove
J M
JM
Martuza
R L
RL
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D016645:Aotidae; D001483:Base Sequence; D001921:Brain; D017931:DNA Primers; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D015316:Genetic Therapy; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D012463:Saliva / Q000821:virology; D013666:Tears / Q000821:virology; D014621:Vagina / Q000378:metabolism / Q000821:virology; D014779:Virus Replication; D017201:Virus Shedding
D000914:Antibodies, Viral; D017931:DNA Primers; D004279:DNA, Viral