2026-05-04T08:31:52Zhttps://riubu.ubu.es/oai/request

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

Cuadrado-Castano, Sara Ayllón Barasoain, Juan Mansour, Mena Iglesia-Vicente, Janis de la Jordan, Stefan Tripathi, Shashank García Sastre, Adolfo Villar, Enrique 2024-09-04T10:40:27Z 2024-09-04T10:40:27Z 2015-05 1535-7163 http://hdl.handle.net/10259/9526 10.1158/1535-7163.MCT-14-0913 1538-8514 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. 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. application/pdf eng American Association for Cancer Research Molecular Cancer Therapeutics. 2015, V. 14, n. 5, p. 1247–1258 https://doi.org/10.1158/1535-7163.MCT-14-0913 info:eu-repo/grantAgreement/NIAID//R01AI088770/US/ info:eu-repo/grantAgreement/ISCIII/Fondo de Investigación Sanitaria/PI08%2F1813/ES/ info:eu-repo/grantAgreement/NCI//5 T32 CA 78207-13/US/ Fas Apoptosis Oncolytic Virotherapy Recombinant virus Medicina Salud Microbiología Medicine Health Microbiology Enhancement of the Proapoptotic Properties of Newcastle Disease Virus Promotes Tumor Remission in Syngeneic Murine Cancer Models info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion info:eu-repo/semantics/openAccess Molecular Cancer Therapeutics 14 5 1247 1258