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

Viruses

Diana Sánchez⁵  Rosana Pelayo⁶  Luis Alberto Medina⁴  Eduardo Vadillo⁶  Rogelio Sánchez¹  Luis Nú༞z⁵  Gabriela Cesarman-Maus³  Rosa Elena Sarmiento-Silva⁵  E. Antonio Chiocca² 

[1] Pathology Department, Spanish Hospital, Mexico City 11520, Mexico;;Faculty of Veterinary Medicine and Animal Husbandry, National Autonomous University of Mexico, Mexico City 04510, Mexico;Hematology Department, National Cancer Institute, Mexico City 14080, MexicoBiomedical Cancer Research Unit, National Cancer Institute and Physics Institute, National Autonomous University of Mexico, Mexico City 14080, Mexico;Faculty of Veterinary Medicine and Animal Husbandry, National Autonomous University of Mexico, Mexico City 04510, Mexico;Medical Research Unit, Oncology Hospital, Mexican Institute for Social Security, Mexico City 06720, Mexico.;

关键词: Newcastle disease virus;    lymphoma;    oncolytic virus;   

DOI  :  10.3390/v8010003

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.