Avian paramyxovirus 4 has potent antitumor activity that surpasses the oncolytic effect of NDV in colon carcinoma and melanoma in vivo models

Abstract Avulaviruses make up some of the most widespread avian viral pathogens. Within the genus, APMV-1, also known as Newcastle disease virus (NDV), is the only avulavirus that has been extensively characterized and explored as an oncolytic agent. While an array of clinical and preclinical studies have shown NDV to hold much promise, the oncolytic potential of the other avulaviruses remains largely unexplored. In this study, we evaluated the in vivo anti-tumor potential of prototype strains of APMV serotypes -2, -3, -4, -6, -7, -8 and -9 in syngeneic B16–F10 melanoma and CT26.WT colon carcinoma models. All the selected viruses were able to delay tumor growth, however, treatment with APMV-4 Duck/Hong Kong/D3/1975 imparted the greatest survival benefit as well as a number of complete remissions that were protected against re-challenge in both tumor models. Infection of cancer cell lines with APMV-4 in vitro resulted in potent activation of the IFN response, and in vivo interrogation of the tumor microenvironment revealed high levels of infiltration by T cells as well as various members of the myeloid compartment. Importantly, the development of a reverse genetics approach to rescue recombinant APMV-4 viruses allowed us to successfully express GFP in the virus backbone, highlighting APMV-4 as a versatile tool that can, in the future, include therapeutic transgenes that will optimize its potential benefit in the clinic. supported in part by a Public Health Service Institutional Research Training Award AI07647