RT info:eu-repo/semantics/article T1 Enhancement of the Proapoptotic Properties of Newcastle Disease Virus Promotes Tumor Remission in Syngeneic Murine Cancer Models A1 Cuadrado-Castano, Sara A1 Ayllón Barasoain, Juan A1 Mansour, Mena A1 Iglesia-Vicente, Janis de la A1 Jordan, Stefan A1 Tripathi, Shashank A1 García Sastre, Adolfo A1 Villar, Enrique K1 Fas K1 Apoptosis K1 Oncolytic K1 Virotherapy K1 Recombinant virus K1 Medicina K1 Medicine K1 Salud K1 Health K1 Microbiología K1 Microbiology AB Newcastle disease virus (NDV) is considered a promising agent for cancer therapy due to its oncolytic properties. These include preferential replication in transformed cells, induction of innate and adaptive immune responses within tumors, and cytopathic effects in infected tumor cells due to the activation of apoptosis. To enhance the latter and thus possibly enhance the overall oncolytic activity of NDV, we generated a recombinant NDV encoding the human TNF receptor Fas (rNDV-B1/Fas). rNDV-B1/Fas replicates to similar titers as its wild-type (rNDV-B1) counterpart; however, overexpression of Fas in infected cells leads to higher levels of cytotoxicity correlated with faster and increased apoptosis responses, in which both the intrinsic and extrinsic pathways are activated earlier. Furthermore, in vivo studies in syngeneic murine melanoma models show an enhancement of the oncolytic properties of rNDV-B1/Fas, with major improvements in survival and tumor remission. Altogether, our data suggest that upregulation of the proapoptotic function of NDV is a viable approach to enhance its antitumor properties and adds to the currently known, rationally based strategies to design optimized therapeutic viral vectors for the treatment of cancer. PB American Association for Cancer Research SN 1535-7163 YR 2015 FD 2015-05 LK http://hdl.handle.net/10259/9526 UL http://hdl.handle.net/10259/9526 LA eng NO R01AI088770 from NIAID to A. García-Sastre and PI08/1813 from the Spanish Fondo de Investigaciones Sanitarias (co-financed by FEDER funds from the EU) to E.Villar. S.Cuadrado-Castano was a predoctoral fellowship holder from the Spanish JCYL (co-financed by European Social Funds (EDU/330/2008; 2008–2012). M. Mansour was supported by NCI 5 T32 CA 78207-13 training grant. DS Repositorio Institucional de la Universidad de Burgos RD 23-nov-2024