Reestablishment of p53/Arf and interferon- β pathways mediated by a novel adenoviral vector potentiates antiviral response and immunogenic cell death

摘要: Late stage melanoma continues to be quite difficult treat and new therapeutic approaches are needed. Since these tumors often retain wild-type p53 have a strong immunogenic potential, we developed gene transfer approach which targets characteristics. Previously, shown that combined of p19Arf interferon-beta (IFNβ) results in higher levels cell death superior immune-mediated antitumor protection. However, experiments were performed using B16 cells (p53wt) with forced expression the adenovirus receptor also mechanism was largely unexplored. Here take advantage novel adenoviral vector (AdRGD-PG), presenting an RGD-modified fiber as well p53-responsive promoter, order investigate further potential benefits mechanisms involved IFNβ genes parental line. Simultaneous is more effective for induction than single treatment revealed can sensitize bystander effect mediated by secreted IFNβ. Strikingly, induced upon activating p53/p19Arf interferon pathways presence AdRGD-PG vectors compared pharmacological mimetics this accompanied upregulation antiviral response genes. Only conferred detection key markers both vitro vivo. Finally, whole-genome transcriptome analysis unique profiles depending on function, including immune activation, virus signaling. In way, cooperation activates pathway elicited IFNβ, culminating death.