Effect of prior exposure to herpes simplex virus 1 on viral vector-mediated tumor therapy in immunocompetent mice

Replication-competent, attenuated mutants of herpes simplex Virus type I (H SV-I) have been shown to be efficacious for tumor therapy. However, these s tudies did not address the consequences of prior exposure to:HSV, as will b e the case with many patients likely to receive this therapy. Two strains o f mice, A/J and BALB/c, were infected with wild-type HSV-I by intraperitone al injection and the immune response was determined by plaque reduction ass ay for neutralizing antibody and ELISA for IgG and IgM. Syngeneic tumors, N 18 neuroblastoma and CT26 colon carcinoma, were implanted subcutaneously in HSV-1 seropositive and naive A/J and BALB/c mice, respectively Established tumors were subsequently treated intratumorally with a multi-mutated HSV-I , G207. G207 inhibited tumor growth to a similar extent whether the mice we re seropositive or not. We next examined the effect of multiple intratumora l inoculations of a IO-fold lower dose of G207 on tumor growth. In the mult iple treatment group (biweekly for 3 weeks), 75% of tumors were cured, wher eas no cures were seen in the single treatment group. We conclude that HSV seropositivity should not deleteriously affect the efficacy of G207 tumor t herapy, and multiple inoculations of virus should be considered for clinica l evaluation.