Fifty Years of Clinical Application of Newcastle Disease Virus: Time to Celebrate!

Abstract

This review provides an overview of 50 years of basic and clinical research on an oncolytic avian virus, Newcastle Disease Virus (NDV), which has particular anti-neoplastic and immune stimulatory properties. Of special interest is the fact that this biological agent induces immunogenic cell death and systemic anti-tumor immunity. Furthermore, localized oncolytic virotherapy with NDV was shown to overcome systemic tumor resistance to immune checkpoint blockade immunotherapy. Clinical experience attests to low side effects and a high safety profile. This is due among others to the strong virus-induced type I interferon response. Other viral characteristics are lack of interaction with host cell DNA, lack of genetic recombination and independence of virus replication from cell proliferation. In this millennium, new recombinant strains of viruses are being produced with improved therapeutic properties. Clinical applications include single case observations, case series studies and Phase I to III studies.

Antitumor and immunostimulatory activities of a genotype V recombinant attenuated veterinary Newcastle disease virus vaccine

“…An approach for this concern is the use of oncolytic viruses, especially NDV, which had demonstrated the capability to kill malignant cells as a result of activation of apoptotic pathways, both in vitro and in vivo (2,27). However, it has been reported that treatment response is dependent on the used NDV strain (2).…”

“…An approach for this concern is the use of oncolytic viruses, especially NDV, which had demonstrated the capability to kill malignant cells as a result of activation of apoptotic pathways, both in vitro and in vivo (2,27). However, it has been reported that treatment response is dependent on the used NDV strain (2). In this sense, our goal was to determine whether a recombinant attenuated NDV from a genotype V velogenic strain (22,24) possesses hemagglutinating, antitumor and immunostimulatory activity.…”

“…Phylogenetic comparison of the full-length HN and F proteins shows two major divisions represented by class I and class II. Class II is further divided into at least 8 (I-VIII) genotypes (8) and genotypes I (such as Ulster) and II (such as La Sota) have the NDV strains most used for virotherapy (2,3). Additionally, NDV is classified into three pathotypes depending on the severity of the disease that it causes in birds: lentogenic (avirulent), mesogenic (intermediate), or velogenic (virulent) (7).…”

“…It is known that in NDV therapy the treatment outcomes are dependent on the kind of tumor and on the used NDV strain (2). Besides, to avoid limiting effects of neutralizing antibodies during virotherapy the use of different NDV strains is considered.…”

“…It is the second leading cause of death globally, and was responsible for 8.8 million deaths in 2015 (1). Conventional chemo and radiotherapy have many adverse effects and fail to cure many types of cancer in humans, thus alternative therapies to treat cancer patients have become more popular since late last century (2). Among these therapies the use of oncolytic viruses, which have tropism to malignant cells but not to normal cells, has been gaining field during the last decades (3) and even a FDA-approved virotherapy is already available since 2015 (IMLYGIC™; Amgen, Inc., Thousand Oaks, CA, USA).…”