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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.

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Acknowledgements

This study was supported by the Virgo consortium, funded by the Dutch government project number FES0908, and by the Netherlands Genomics Initiative (NGI) project number 050-060-452. We thank B Peeters (Central Veterinary Institute of Wageningen UR, Lelystad, the Netherlands) for providing plasmids for recombinant NDV. We thank T Leighton (Canadian Cooperative Wildlife Health Centre, Saskatoon, Canada) for providing a positive control NDV-infected tissue. We thank V Vaes and D de Meulder (EDC Erasmus MC, Rotterdam, the Netherlands) for assisting with animal housing and experiments.

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Correspondence to B G van den Hoogen.

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Buijs, P., van Amerongen, G., van Nieuwkoop, S. et al. Intravenously injected Newcastle disease virus in non-human primates is safe to use for oncolytic virotherapy. Cancer Gene Ther 21, 463–471 (2014). https://doi.org/10.1038/cgt.2014.51

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