Effect of preexisting anti-herpes immunity on the efficacy of herpes simplex viral therapy in a murine intraperitoneal tumor model

HSV-1716, a replicating nonneurovirulent herpes simplex virus type 1, has s hown efficacy in treating multiple types of human tumors in immunodeficient mice. Since the majority of the human population has been previously expos ed to herpes simplex virus, the efficacy of HSV-based oncolytic therapy was investigated in an immunocompetent animal tumor model. EJ-6-2-Bam-6a, a tu mor cell line derived from h-ras-transformed murine fibroblast, exhibit a d iffuse growth pattern in the peritoneal cavity of BALB/c mice and replicate HSV-1716 to titers observed in human tumors. An established intraperitonea l (ip) tumor model of EJ-6-2-Bam-6a in naive and HSV-immunized mice was use d to evaluate the efficacy of single or multiple ip administrations of HSV- 1716 (4 X 10(6) pfu/treatment) or of carrier cells, which are irradiated, e x vivo virally infected EJ-6-2-Bam-6a cells that can amplify the viral load in situ. All treated groups significantly prolonged survival versus media control with an approximately 40% long-term survival rate (cure) in the mul tiply treated, HSV-naive animals. Prior immunization of the mice with HSV d id not significantly decrease the median survival of the single or multiply treated HSV-1716 or the carrier cell-treated groups. These studies support the development of replication-selective herpes virus mutants for use in l ocalized intraperitoneal malignancies.