Newcastle Disease Virus: Potential Therapeutic Application for Human and Canine Lymphoma

Abstract

Research on oncolytic viruses has mostly been directed towards the treatment of solid tumors, which has yielded limited information regarding their activity in hematological cancer. It has also been directed towards the treatment of humans, yet veterinary medicine may also benefit. Several strains of the Newcastle disease virus (NDV) have been used as oncolytics in vitro and in a number of in vivo experiments. We studied the cytolytic effect of NDV-MLS, a low virulence attenuated lentogenic strain, on a human large B-cell lymphoma cell line (SU-DHL-4), as well as on primary canine-derived B-cell lymphoma cells, and compared them to healthy peripheral blood mononuclear cells (PBMC) from both humans and dogs. NDV-MLS reduced cell survival in both human (42% ± 5%) and dog (34% ± 12%) lymphoma cells as compared to untreated controls. No significant effect on PBMC was seen. Cell death involved apoptosis as documented by flow-cytometry. NDV-MLS infections of malignant lymphoma tumors in vivo in dogs were confirmed by electron microscopy. Early (24 h) biodistribution of intravenous injection of 1 × 1012 TCID50 (tissue culture infective dose) in a dog with T-cell lymphoma showed viral localization only in the kidney, the salivary gland, the lung and the stomach by immunohistochemistry and/or endpoint PCR. We conclude that NDV-MLS may be a promising agent for the treatment of lymphomas. Future research is needed to elucidate the optimal therapeutic regimen and establish appropriate biosafety measures.

Oncolytic Viruses for Canine Cancer Treatment

“…This virus showed natural oncolytic effects, principally in cells derived from human solid tumors [ 68 , 69 , 70 ]. A lentogenic strain was evaluated in canine cancer cells in vitro and in a dog with a spontaneous cancer [ 71 , 72 ]. In vitro, the NDV-MLS strain was preferentially toxic for canine malignant cells versus healthy PBMCs.…”

“…In vitro, the NDV-MLS strain was preferentially toxic for canine malignant cells versus healthy PBMCs. The virus decreased the viability of primary canine B lymphoma cells by close to 40% [ 72 ]. In this same study, the early viral biodistribution was evaluated in a dog with a spontaneous T-cell lymphoma, 24 h after the intravenous (IV) administration of 1 × 10 12 median tissue culture infectious dose (TCID 50 ).…”

“…In this same study, the early viral biodistribution was evaluated in a dog with a spontaneous T-cell lymphoma, 24 h after the intravenous (IV) administration of 1 × 10 12 median tissue culture infectious dose (TCID 50 ). Viral dissemination was detected by PCR only in healthy kidney, salivary gland, lung, and stomach, but not in tumor tissue, with no abnormalities upon histopathological assessment [ 72 ]. Interestingly, a complete long-term response in a dog with an aggressive chemotherapy-unresponsive lymphoma was reported [ 71 ].…”

Oncolytic Viruses and Hematological Malignancies: A New Class of Immunotherapy Drugs

“…No relevant action on PBMC was demonstrated. Destruction of cells was due to programmed cell death as supported by flow-cytometry [ 126 ]. Eaton et al proved an oncolytic action of NDV in vivo.…”

Sialoglycovirology of Lectins: Sialyl Glycan Binding of Enveloped and Non-enveloped Viruses

“…(3) There is a Chinese saying "use the enemy to kill the enemy." Some Sia-binding viruses, such as NDV [188], reoviruses [189], adenovirus vectors pseudotyped with fibers from HAdV-D [190], and AAVs [191], have been investigated for treatment of human diseases. Based on their oncolytic properties that preferentially infect and lyse cancer cells (so-called oncolytic virotherapy), reovirus T3D has been developed to be pelareorep (Reolysin ® ), which was approved by the FDA in 2015 for treatment of malignant glioma and in 2017 for treatment of metastatic breast cancer.…”