Intravenously injected Newcastle disease virus in non-human primates is safe to use for oncolytic virotherapy

Cancer Gene Ther. 2014 Nov;21(11):463-71. doi: 10.1038/cgt.2014.51. Epub 2014 Sep 26.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allantois / virology
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Agents / toxicity*
  • Cell Line
  • Chick Embryo
  • DNA, Complementary / genetics
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Injections, Intravenous
  • Macaca fascicularis
  • Male
  • Mutagenesis, Site-Directed
  • Neutralization Tests
  • Newcastle disease virus / genetics*
  • Oncolytic Virotherapy / methods*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Viral Vaccines / administration & dosage
  • Virus Shedding

Substances

  • Antineoplastic Agents
  • DNA, Complementary
  • Viral Vaccines