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.

Oncolytic Newcastle disease virus expressing chimeric antibody enhanced anti-tumor efficacy in orthotopic hepatoma-bearing mice

“…The virus is regarded as a natural OV for solid tumor therapy in clinic trials and shows minimal side-effects with systemic administration [ 3 , 4 ]. Recently, the toxicity, biodistribution, and shedding of NDV in non-human primates under intravenous injection were evaluated, demonstrating the safety for intravenous administration [ 5 ].…”

Proinflammatory response induced by Newcastle disease virus in tumor and normal cells

“…The efficacy, safety and tumor selectivity have been the rationales of using NDV as antitumor agent 3,12,13,21,28,31. In this study, to demonstrate the cytotoxicity and tumor selectivity of NDV, we utilized a lentogenic LaSota strain, which has been long used as a vaccine strain worldwide, at low MOI.…”

“…This virus has been reported to be an effective oncolytic agent in vitro and in vivo against many types of solid tumors such as hepatocellular carcinoma, pancreatic adenocarcinoma, melanoma, pleural mesothelioma, colorectal carcinoma, renal carcinoma, glioblastoma and many others,5,7–13 as well as in clinical studies in patients with glioblastoma multiforme, colorectal carcinoma, non-small cell lung carcinoma, renal carcinoma, breast adenocarcinoma, mesothelioma and pancreatic adenocarcinoma 14–18. NDV causes a disease that predominantly affects poultry, although infection in humans has been reported to cause conjunctivitis19,20 and/or mild flu-like symptoms 13–17,21. Based on their virulence on birds, NDV strains can be divided into three groups: lentogenic (low virulence), mesogenic (medium virulence) and velogenic (high virulence).…”

Oncolytic viruses: From bench to bedside with a focus on safety

“…administration of the virus to be safe without relevant toxicity of high dosages, although relevant shedding was noted. 87 Family Rhabdoviridae: Vesicular Stomatitis Virus (VSV)…”