OncoVEX: A family of oncolytic herpes simplex viruses optimised for therapeutic use

2601 Background: HSV in which ICP34.5 is inactivated directs tumour selective cell lysis in vitro and in vivo. Such viruses have proven safe in Phase I clinical trials by intra-tumoral injection in glioma and melanoma patients. Oncolytic HSV containing an active gene has not previously been tested in man. Methods: Previous work has used serially passaged isolates of HSV-1 which are attenuated in human tumour cells compared to clinical isolates. To produce improved viruses, we have deleted ICP34.5 from clinical isolates of HSV-1. This greatly enhanced tumour cell killing. One of these viruses was further deleted for ICP47 (which blocks antigen presentation) and GM-CSF was inserted. This aimed to maximize anti-tumour immune responses following injection and provide an in situ, patient-specific, anti-tumour vaccine, combined with oncolysis. Results: The anti-tumour properties of the virus were greatly improved by each of the modifications made. In vivo, both injected and non-injected tumours were cured and a...