*6.4. VSV Encoding p53 Transgenes*

Studies suggest that p53 enhances type 1 IFN signaling in normal cells and in some cancer cells types. However, our recent study demonstrated that VSV-encoded p53 trasngene actually inhibited antiviral signaling in PDAC cells, while stimulating VSV-∆M51 replication in those cells [57]. Several potential reasons exist for the contrast to previous reports, including (1) differences between normal cells and different cancer cells in antiviral signaling, (2) constitutive activation of NF-κB pathway in a majority of PDACs, and (3) different timing and level of expression for VSV-encoded p53 in the cell lines used in this study. Future studies with VSVs expressing human p53 in animal models will determine if the oncoselective phenotype seen in PDAC cell lines is also observed in vivo, as it is necessary to see if the benefits are retained in an immunocompetent model without compromising safety.
