2026-04-23T00:01:58Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/95262024-09-05T00:05:21Zcom_10259_4862com_10259_5086com_10259_2604col_10259_4863

00925njm 22002777a 4500 dc Cuadrado-Castano, Sara author Ayllón Barasoain, Juan author Mansour, Mena author Iglesia-Vicente, Janis de la author Jordan, Stefan author Tripathi, Shashank author García Sastre, Adolfo author Villar, Enrique author 2015-05 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. 1535-7163 http://hdl.handle.net/10259/9526 10.1158/1535-7163.MCT-14-0913 1538-8514 Fas Apoptosis Oncolytic Virotherapy Recombinant virus Enhancement of the Proapoptotic Properties of Newcastle Disease Virus Promotes Tumor Remission in Syngeneic Murine Cancer Models