Molecular Mechanisms of Anti-Neoplastic and Immune Stimulatory Properties of Oncolytic Newcastle Disease Virus

Abstract

Oncolytic viruses represent interesting anti-cancer agents with high tumor selectivity and immune stimulatory potential. The present review provides an update of the molecular mechanisms of the anti-neoplastic and immune stimulatory properties of the avian paramyxovirus, Newcastle Disease Virus (NDV). The anti-neoplastic activities of NDV include (i) the endocytic targeting of the GTPase Rac1 in Ras-transformed human tumorigenic cells; (ii) the switch from cellular protein to viral protein synthesis and the induction of autophagy mediated by viral nucleoprotein NP; (iii) the virus replication mediated by viral RNA polymerase (large protein (L), associated with phosphoprotein (P)); (iv) the facilitation of NDV spread in tumors via the membrane budding of the virus progeny with the help of matrix protein (M) and fusion protein (F); and (v) the oncolysis via apoptosis, necroptosis, pyroptosis, or ferroptosis associated with immunogenic cell death. A special property of this oncolytic virus consists of its potential for breaking therapy resistance in human cancer cells. Eight examples of this important property are presented and explained. In healthy human cells, NDV infection activates the RIG-MAVs immune signaling pathway and establishes an anti-viral state based on a strong and uninhibited interferon α,ß response. The review also describes the molecular determinants and mechanisms of the NDV-mediated immune stimulatory effects, in which the viral hemagglutinin-neuraminidase (HN) protein plays a prominent role. The six viral proteins provide oncolytic NDV with a special profile in the treatment of cancer.

Oncolytic virotherapy: basic principles, recent advances and future directions

“… 149 The oAds-armed apoptotic protein, encoded by the VP3 gene of chicken anemia virus (CAV), induces pyroptosis by cleaving caspase-3 and GSDME, and significantly inhibits the growth of colorectal tumors. 150 Other OVs, such as coxsackievirus B3, 151 HSV-1, 152 NDV, 153 etc., have also adopted the death mode, and these pyroptosis-based anticancer drugs may open up new possibilities for OV therapy in the future.…”

Oncolytic Virus‐Driven Biotherapies from Bench to Bedside

“…[ 168 ] Similar to other paramyxoviruses in the family, the genome of NDV encodes six proteins, namely, the nucleocapsid protein, hemagglutinin‐neuraminidase, phosphoprotein, RNA‐dependent RNA polymerase, fusion protein, and matrix protein. [ 169 ] The NDV genome also has a large capacity (>5 kb), making it capable of facilitating gene modifications. NDV binds to the host cell surface via the neuraminidase receptor or sialoglyco conjugates and subsequently invades the cell through endocytosis or pH‐independent fusion.…”

Immunotherapy: A new target for cancer cure (Review)

“…Currently, a large body of evidence suggests that oncolytic virus therapy induces tumor cell death by enhancing the antigenicity of tumor cells or their susceptibility to immune cells when used in combination with radiotherapy, chemotherapy and other immunotherapies ( 154 , 155 ). Many naturally occurring viruses, such as parvovirus, measles virus, reovirus and Newcastle disease virus, exhibit a natural preference for cancer cells ( 156 ). However, other viruses such as adenovirus, vesicular stomatitis and vaccinia virus and HSV need to be engineered to be cancer specific ( Table I ).…”