Internalization of oncolytic reovirus by XXXX dendritic cell carriers protects the virus from neutralization.

@entity1 @entity5 @entity320 @entity3
PURPOSE: Dendritic cells (DC) may be the most effective way of delivering oncolytic viruses to @entity1 . Reovirus, a naturally occurring oncolytic virus, is currently undergoing early clinical trials; however, intravenous delivery of the virus is hampered by pre-existing antiviral immunity. Systemic delivery via cell carriage is a novel approach currently under investigation and initial studies have indicated its feasibility by using a variety of cell types and viruses. This study addressed the efficacy of @entity1 DC to transport virus in the presence of human neutralizing serum. EXPERIMENTAL DESIGN: Following reovirus-loading, DC or T cells were cocultured with @entity320 cells with or without neutralizing serum; the @entity320 cells were then analyzed for cell death. Following reovirus loading, cells were examined by electron microscopy to identify mechanisms of delivery. The phagocytic function of reovirus-loaded DC was investigated by using labeled @entity5 cells and the ability of reovirus-loaded DC to prime T cells was also investigated. RESULTS: In the presence of human neutralizing serum DC, but not T cells, were able to deliver reovirus for @entity320 cell killing in vitro. Electron microscopy suggested that DC protected the virus by internalization, whereas with T cells it remained bound to the surface and hence accessible to neutralizing antibodies. Furthermore, DC loaded with reovirus were fully functional with regard to phagocytosis and priming of specific antitumor immune responses. CONCLUSIONS: The delivery of reovirus via DC could be a promising new approach offering the possibility of combining systemic viral therapy for @entity3 with induction of an antitumor immune response.
