Search

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.

Prostate adenocarcinoma is the most common nonskin malignancy in males and the second most common cause of cancer death in the United States (Landis et al., 1998). Initial treatments of surgery or radiotherapy may cause impotence and/or incontinence from neural damage (Eastham and Scardino, 1998; Porter et al., 1998). When extraprostatic or metastatic disease develops, castration or pharmaceutical androgen ablation is utilized (Catalona, 1994). Androgen-resistant recurrence indicates a poor prognosis and justifies experimental chemotherapy (Oh and Kantoff, 1998). G207 (Mineta et al., 1995; Yazaki et al., 1995) is a multimutated herpes simplex virus 1 (HSV) vector that replicates within cancer cells, causing cellular death; however, replication is limited in normal cells, including those of the nervous system. In vitro, G207 at a low multiplicity of infection (MOI of 0.01) is oncolytic for multiple human prostate cancer cells. In athymic mice, a single intraneoplastic inoculation of G207 completely eradicates22% of established subcutaneous human prostate cancer tumors irrespective of hormonal responsiveness. Two intraneoplastic inoculations of G207 completely eradicated two of three recurrent previously irradiated tumors and two intravenous administration of G207 induced tumor regression in distant subcutaneous tumors and completely eradicated one-fourth of the tumors.