Avian Paramyxovirus 4 Antitumor Activity Check for updates Leads to Complete Remissions and Long-term Protective Memory in Preclinical Melanoma and Colon Carcinoma Models

Abstract

Avulaviruses represent a diverse subfamily of nonsegmented negative- have identified APMV-4 Duck/Hong Kong/D3/1975 virus as a novel on-strand RNA viruses infecting avian species worldwide. To date, 22 different colytic agent with greater therapeutic potential than one of the NDV clinical serotypes have been identified in a variety of avian hosts, including wild and candidate strains, La Sota. Intratumoral administration of the naturally ocdomestic birds. APMV-1 (Avian Paramyxovirus 1), also known as Newcas- curring APMV-4 virus significantly extends survival, promotes complete tle disease virus (NDV), is the only avulavirus that has been extensively remission, and confers protection against rechallenge in both murine colon characterized because of its relevance for the poultry industry and, more carcinoma and melanoma tumor models. Furthermore, we have designed recently, its inherent oncolytic activity and potential as a cancer thera- a plasmid rescue strategy that allows us to develop recombinant APMV-4–peutic. An array of both naturally occurring and recombinant APMV-1 based viruses. The infectious clone rAPMV-4 preserves the extraordinary strains has been tested in different preclinical models and clinical trials, antitumor capacity of its natural counterpart, paving the way to a promising highlighting NDV as a promising viral agent for human cancer therapy. next generation of viral therapeutics. To date, the oncolytic potential of other closely related avulaviruses re- Significance:Discovery of the oncolytic properties of APMV-4 mains unknown. Here, we have examined the in vivo antitumor capability Duck/Hong Kong/D3/1975: a novel cancer therapeutic with natural ca-of prototype strains of APMV serotypes -2 -3, -4, -6, -7, -8, and -9 in syn- pacity to exert complete remission and long-term antitumor protection in geneic murine colon carcinoma and melanoma tumor models. Our studies syngeneic mouse cancer models.