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Newcastle Disease Virus: Potential Therapeutic Application for Human and Canine Lymphoma
Diana Sánchez1, Rosana Pelayo2, Luis Alberto Medina3
1Faculty of Veterinary Medicine and Animal Husbandry, National Autonomous University of Mexico, Mexico City 04510, Mexico. dianasanchezc@hotmail.com.
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 × 10(12) 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.
Insights
Newcastle disease virus (NDV)-MLS effectively reduced lymphoma cell survival in both human and canine models, inducing apoptosis without harming healthy cells. This oncolytic virus shows promise for treating B-cell lymphomas.
Area of Science:
- Oncolytic virology
- Veterinary oncology
- Immunotherapy
Background:
- Oncolytic virus research primarily targets solid tumors, with limited data on hematological cancers.
- Newcastle disease virus (NDV) strains have demonstrated oncolytic potential in preclinical studies.
- Veterinary applications of oncolytic viruses remain largely unexplored.
Purpose of the Study:
- To evaluate the cytolytic efficacy of the attenuated NDV-MLS strain against human and canine lymphoma cell lines.
- To compare the effects of NDV-MLS on malignant cells versus healthy peripheral blood mononuclear cells (PBMCs) in both species.
- To investigate the in vivo biodistribution and tumor localization of NDV-MLS in a canine lymphoma model.
Main Methods:
- In vitro cytolytic assays on human large B-cell lymphoma (SU-DHL-4) and primary canine lymphoma cells.
- Comparison with healthy human and canine PBMCs.
- Flow cytometry to detect apoptosis.
- In vivo studies in dogs with lymphoma, including immunohistochemistry and PCR for viral detection.
Main Results:
- NDV-MLS significantly reduced lymphoma cell viability by 42% in human and 34% in canine cells.
- No significant impact on healthy PBMCs from either species was observed.
- Apoptosis was confirmed as the mechanism of cell death.
- In vivo studies confirmed viral presence in lymphoma tumors and identified early biodistribution patterns.
Conclusions:
- NDV-MLS exhibits selective oncolytic activity against B-cell lymphomas in vitro and in vivo.
- The virus is well-tolerated by healthy PBMCs, suggesting a favorable safety profile.
- NDV-MLS represents a promising candidate for further development as an oncolytic therapy for lymphomas in both human and veterinary medicine.
