title: Intravenously injected Newcastle disease virus in non-human primates is safe to use for oncolytic virotherapy.
abstract: Newcastle disease virus (NDV) is an avian paramyxovirus with oncolytic potential. Detailed preclinical information regarding the safety of oncolytic NDV is scarce. In this study, we evaluated the toxicity, biodistribution and shedding of intravenously injected oncolytic NDVs in non-human primates (Macaca fascicularis). Two animals were injected with escalating doses of a non-recombinant vaccine strain, a recombinant lentogenic strain or a recombinant mesogenic strain. To study transmission, naive animals were co-housed with the injected animals. Injection with NDV did not lead to severe illness in the animals or abnormalities in hematologic or biochemistry measurements. Injected animals shed low amounts of virus, but this did not lead to seroconversion of the contact animals. Postmortem evaluation demonstrated no pathological changes or evidence of virus replication. This study demonstrates that NDV generated in embryonated chicken eggs is safe for intravenous administration to non-human primates. In addition, our study confirmed results from a previous report that naïve primate and human sera are able to neutralize egg-generated NDV. We discuss the implications of these results for our study and the use of NDV for virotherapy.
authors.affiliation: Department of Surgery, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: P R A
authors.initials: PR
authors.lastname: Buijs
authors.affiliation: Viroclinics Biosciences, BV, Rotterdam, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: van Amerongen
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: van Nieuwkoop
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: T M
authors.initials: TM
authors.lastname: Bestebroer
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: P R W A
authors.initials: PR
authors.lastname: van Run
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Kuiken
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: R A M
authors.initials: RA
authors.lastname: Fouchier
authors.affiliation: Department of Surgery, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: C H J
authors.initials: CH
authors.lastname: van Eijck
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: B G
authors.initials: BG
authors.lastname: van den Hoogen
mesh_terms: D000482:Allantois / Q000821:virology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D002460:Cell Line; D002642:Chick Embryo; D018076:DNA, Complementary / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D007275:Injections, Intravenous; D008252:Macaca fascicularis; D008297:Male; D016297:Mutagenesis, Site-Directed; D009500:Neutralization Tests; D009522:Newcastle disease virus / Q000235:genetics*; D050130:Oncolytic Virotherapy / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014765:Viral Vaccines / Q000008:administration & dosage; D017201:Virus Shedding
chemical_list: D000970:Antineoplastic Agents; D018076:DNA, Complementary; D014765:Viral Vaccines