Enhancement of the proapoptotic properties of newcastle disease virus promotes tumor remission in syngeneic murine cancer models

Sara Cuadrado-Castano, Juan Ayllon, Mena Mansour, Janis De La Iglesia-Vicente, Stefan Jordan, Shashank Tripathi, Adolfo García-Sastre, Enrique Villar

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1247-1258
Number of pages12
JournalMolecular Cancer Therapeutics
Volume14
Issue number5
DOIs
StatePublished - May 1 2015

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