Newcastle Disease Virus at the Forefront of Cancer Immunotherapy

Abstract

Preclinical and clinical studies dating back to the 1950s have demonstrated that Newcastle disease virus (NDV) has oncolytic properties and can potently stimulate antitumor immune responses. NDV selectively infects, replicates within, and lyses cancer cells by exploiting defective antiviral defenses in cancer cells. Inflammation within the tumor microenvironment in response to NDV leads to the recruitment of innate and adaptive immune effector cells, presentation of tumor antigens, and induction of immune checkpoints. In animal models, intratumoral injection of NDV results in T cell infiltration of both local and distant non-injected tumors, demonstrating the potential of NDV to activate systemic adaptive antitumor immunity. The combination of intratumoral NDV with systemic immune checkpoint blockade leads to regression of both injected and distant tumors, an effect further potentiated by introduction of immunomodulatory transgenes into the viral genome. Clinical trials with naturally occurring NDV administered intravenously demonstrated durable responses across numerous cancer types. Based on these studies, further exploration of NDV is warranted, and clinical studies using recombinant NDV in combination with immune checkpoint blockade have been initiated.

Development and pre-clinical evaluation of Newcastle disease virus-vectored SARS-CoV-2 intranasal vaccine candidate

“…In tumoral cells, NDV replicates in the intra cellular environment with a cytotoxic, necrotic effect or an auto phagocytosis mechanism. Thus, the NVD achieves control in cancer cells, stimulating immunity against tumors 45,93 . It has been shown that NDV is non-pathogenic to humans as it has been used as a treatment against multiple types of cancer without causing serious adverse effects 45,93 .…”

“…It has been shown that NDV is non-pathogenic to humans as it has been used as a treatment against multiple types of cancer without causing serious adverse effects 45,93 . In vitro studies in breast, kidney, bone, skin, brain and cervical cancer cells show that NDV causes cancer cell reduction by activating extrinsic and intrinsic pathways of apoptosis 45,[94][95][96][97] . Clinical trials with rNDV have been developed over the years, and more than a dozen of studies have been reported in which lytic NDV strains have been inoculated .…”

“…It is made The copyright holder for this preprint this version posted March 8, 2021. ; https://doi.org/10.1101/2021.03.07.434276 doi: bioRxiv preprint intravenously, intratumorally or intramuscularly, for example, against colon cancer that have reached phase III, increasing the years of life to 7, among volunteers without side effects 48 . Likewise, phase I has been carried out with patients with chronic cancer with the mesogenic strain rNDV PV701, resulting in the survival of volunteers with up to two more years of life 45 . The rNDV has also been tested in phase I and II against malignant gliomas, where the doses inoculated intravenously for 5 consecutive days ranged at concentrations of 0.1, 0.32, 0.93, 5.9, and 11 BIU of NDV-HUJ in which patients presented a mid-fever as a side effect that was controlled after a few days 43,45 .…”

“…NDV has selectivity for tumors, acting as an oncolytic virus. Tumoral cell defects, including anti-viral and apoptotic pathways 44 , explain the NDV-mediated oncolytic efficiency in mammal cells, through manipulation of antiviral cellular pathways, induction of apoptosis, and indirect activation of the innate and adaptive immune response (humoral, cellular and mucosal) 32,45,46 . The use of oncolytic viruses for cancer treatment in humans have not shown serious side effects unlike other systemic cancer therapies, in extreme cases there could cause mild fever and conjunctivitis 44 .…”

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

“…NDV selectively infects, and lyses tumor cells by exploiting defective antiviral defenses in cancer cells. Inflammation within the tumor microenvironment in response to NDV leads to the recruitment of innate and adaptive immune effector cells, presentation of tumor antigens, and induction of immune checkpoints [ 39 ].…”