title: Isolation of more potent oncolytic paramyxovirus by bioselection.
abstract: Newcastle disease virus (NDV) is an oncolytic paramyxovirus with a nonsegmented single-stranded RNA genome. In this report, a recombinant oncolytic NDV was passaged in human tumor xenografts and reisolated and characterized after two rounds of bioselection. Several isolates could be recovered that differed from the parental virus with respect to virus spread in tumor cells and the ability to form syncytia in human tumor cells. Three isolates were identified that demonstrated superior oncolytic potency compared with the parental virus as measured by increased oncolytic potency in confluent tumor cell monolayers, in tumor cell spheroids and in a mouse xenograft tumor model. The surface proteins F and HN were sequence analyzed and characterized for fusogenicity. The present study demonstrates that in vivo NDV bioselection can enable the isolation of novel, oncolytic NDV and thus represents a powerful methodology for the development of highly potent oncolytic viruses.
authors.affiliation: Therapeutic Research Group Oncology, Bayer Pharma AG, Berlin, Germany. Rudolf.Beier@Bayer.com
authors.forename: R
authors.initials: R
authors.lastname: Beier
authors.forename: T
authors.initials: T
authors.lastname: Hermiston
authors.forename: D
authors.initials: D
authors.lastname: Mumberg
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015726:Giant Cells; D006388:Hemagglutinins / Q000235:genetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009522:Newcastle disease virus / Q000235:genetics* / Q000302:isolation & purification; D050504:Oncolytic Viruses / Q000235:genetics* / Q000302:isolation & purification; D012641:Selection, Genetic; D014183:Transplantation, Heterologous; D014760:Viral Fusion Proteins / Q000235:genetics
chemical_list: D006388:Hemagglutinins; D014760:Viral Fusion Proteins