Semin Immunol. 2026 May 19;82:102032. doi: 10.1016/j.smim.2026.102032. Online ahead of print.
ABSTRACT
Oncolytic virotherapy emerged as a revolutionary approach to immunotherapy in cancer treatment. Newcastle disease virus (NDV), a promising oncolytic agent of the Paramyxoviridae family, has gained considerable attention as an immunotherapeutic agent against cancer mainly due to its inherent tumor selectivity, broad tropism, convenient propagation, and lack of pre-existing immunity in humans. Its selective tropism is primarily mediated by an impaired type I interferon signalling pathway in cancer cells. Apart from the direct lysis, NDV induces immunogenic cell death (ICD), releasing tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs), which in turn lead to potent activation of innate and acquired immunity. The efficiency of the wild-type NDV strains has been improved through genetic engineering. Recombinant strains capable of expressing immuno-stimulatory cytokines and enzymes to remodel the immuno-suppressive tumor microenvironment (TME) are the most promising. This review discusses the history of early events that shaped NDV into an ‘oncolytic agent’. It reviews its characteristics and mechanisms of anti-tumor activity, which can directly or indirectly form part of the cancer immunity cycle. Further, limitations and issues surrounding the unmet translational delay of NDV as an immuno-therapeutic agent in personalized and combination immunotherapy strategies are also discussed.
PMID:42155154 | DOI:10.1016/j.smim.2026.102032