4.7 Article

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

期刊

BIOMEDICINES
卷 10, 期 3, 页码 -

出版社

MDPI
DOI: 10.3390/biomedicines10030562

关键词

autophagy; cancer immunotherapy; cancer vaccine; cancer therapy resistance; dendritic cell; exosome; immunogenic cell death; interferon-I; NK cell; T cell

资金

  1. IOZK foundation

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This review provides an update on the molecular mechanisms of the avian paramyxovirus, Newcastle Disease Virus (NDV), in its anti-neoplastic and immune stimulatory properties. It highlights the potential of NDV as a unique oncolytic virus that can overcome therapy resistance in human cancer cells.
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 alpha,beta 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.

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