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Preclinical safety evaluation of G207, a replication-competent herpes simplex virus type 1, inoculated
S Varghese1, J T Newsome, S D Rabkin
1Molecular Neurosurgery Laboratory, Department of Surgery (Neurosurgery), Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Abstract:
G207, a replication-competent herpes simplex virus type 1 (HSV-1) virus, has been previously shown to be effective against human prostate cancer xenografts in mice. This study assesses its safety in the prostate of two animal models known for their sensitivity to HSV-1. BALB/c mice were injected intraprostatically with either HSV-1 G207 or strain F and observed for 5 months. None of the G207-injected animals exhibited any clinical signs of disease or died. However, 50% of strain F-injected mice displayed sluggish, hunched behavior and died by day 13. Histopathologically, the G207-injected prostates were normal whereas strain F-injected prostates showed epithelial flattening, sloughing, and stromal edema. Four Aotus nancymae monkeys were also injected with G207 intraprostatically and observed short term (up to 21 days) and long term (56 days). Safety was assessed on the basis of clinical observations, viral biodistribution, virus shedding, and histopathology. None of the injected monkeys displayed evidence of clinical disease, shedding of infectious virus, or spread of the virus into other organs. Except for minor histological changes unrelated to the study, no significant abnormalities were observed. These results demonstrate that G207 can be safely inoculated into the prostate and should be considered for human trials for the treatment of prostate cancer.
Insights
Herpes simplex virus type 1 (HSV-1) G207 is safe for prostate cancer treatment. Studies in mice and monkeys show G207 has no adverse effects, unlike other HSV-1 strains, supporting its use in human trials.
Area of Science:
- Oncolytic virology
- Viral immunotherapy
- Prostate cancer research
Background:
- Replication-competent herpes simplex virus type 1 (HSV-1) G207 demonstrates efficacy against prostate cancer xenografts.
- HSV-1 strains can exhibit varying safety profiles in sensitive animal models.
Purpose of the Study:
- To evaluate the safety of intraprostatic inoculation of HSV-1 G207 in animal models.
- To compare the safety of G207 with a control HSV-1 strain in mice.
- To assess the short-term and long-term safety of G207 in non-human primates.
Main Methods:
- Intraprostatic injection of HSV-1 G207 or strain F into BALB/c mice, with 5-month observation.
- Intraprostatic injection of HSV-1 G207 into Aotus nancymae monkeys, with 21-day and 56-day observations.
- Safety assessment included clinical signs, mortality, viral shedding, biodistribution, and histopathology.
Main Results:
- No G207-injected mice showed disease or died; strain F caused mortality in 50% of mice.
- G207-injected prostates in mice remained histopathologically normal, unlike strain F-injected prostates.
- Monkeys injected with G207 showed no clinical disease, viral shedding, or organ spread; minor unrelated histological changes were noted.
Conclusions:
- HSV-1 G207 can be safely inoculated into the prostate.
- The safety profile supports the consideration of G207 for human clinical trials in prostate cancer treatment.
- G207 represents a promising oncolytic virus for prostate cancer therapy.

