TREATMENT OF SPONTANEOUSLY ARISING RETINOBLASTOMA TUMORS IN TRANSGENIC MICE WITH AN ATTENUATED HERPES-SIMPLEX VIRUS MUTANT

The use of viruses to treat tumors has received renewed interest with the availability of genetically defined attenuated mutants. Herpes sim plex virus (HSV) type 1 in particular has been shown to be effective f or tumors of neuronal origin. However, the model systems used for thes e studies rely on the use of explanted tumor cells in immunodeficient animals. We have used a recently developed transgenic mouse model, whe rein mice spontaneously develop retinoblastomas, to determine if a mut ant HSV has a therapeutic effect against an endogenously arising tumor in an immunocompetent host. The injection of 1 x 10(6) PFU of the neu roattenuated HSV-1/HSV-2 recombinant RE6 into the vitreous of transgen ic mice resulted in a significant inhibition of tumor growth compared to injection of medium alone (P = 0.0063). Immunohistochemical analysi s of viral antigen showed that viral replication was restricted to foc al areas of the tumors and the retinal pigment epithelium. Viral growt h was not significantly different in the eyes of transgene-positive an d transgene-negative mice, suggesting that enhanced replication in tum or cells may not explain the effects. Tumor cells in the treated eyes were significantly less differentiated than those in the untreated eye s (P = 0.04), suggesting that the virus may replicate better in certai n cell types in the tumors. Although the injection of RE6 resulted in a difference in tumor size, the treatment did not result in the elimin ation of tumors in any of the mice. Improvements in the efficacy of tu mor control are needed if this therapy is to be of use. (C) 1997 Acade mic Press.