Re-engineering vesicular stomatitis virus to abrogate neurotoxicity, circumvent humoral immunity and enhance oncolytic potency
Menée sur des lignées cellulaires et à l'aide de modèles murins, cette étude évalue l'activitié antitumorale et la neurotoxicité d'un virus oncolytique élaboré à partir du virus de la stomatite vésiculaire
As cancer treatment tools, oncolytic viruses (OV) have yet to realize what some see as their ultimate clinical potential. In this study, we have engineered a chimeric vesicular stomatitis virus (VSV) that is devoid of its natural neurotoxicity while retaining potent oncolytic activity. The envelope glycoprotein (G) of VSV was replaced with a variant glycoprotein of the lymphocytic choriomeningitis virus (LCMV-GP) creating a replicating therapeutic, rVSV(GP), that is benign in normal brain but can effectively eliminate brain cancer in multiple pre-clinical tumour models in vivo. Furthermore, it can be safely administered systemically to mice and displays greater potency against a spectrum of human cancer cell lines than current OV candidates. Remarkably, rVSV(GP) escapes humoral immunity, thus, for the first time, allowing repeated systemic OV application without loss of therapeutic efficacy. Taken together, rVSV(GP) offers a considerably improved OV platform which lacks several of the major drawbacks that have limited the clinical potential of this technology to date.
Cancer Research 2014