The present invention includes the Paramyxovirus Parainfluenza Virus 5 (PIV5) as an oncolytic agent for treating various cancers, including, but not limited to breast cancer, lung cancer and melanoma. PIV5 oncolytic agents include both wild type PIV5 and various recombinant PIV5 constructs. Recombinant PIV5 constructs may include PIV5 lacking the conserved C-terminus of the V protein (PIV5VΔ；C), PIV5 with mutations in the N-terminus of the V/P protein (PIV5CPI−；), and PIV5 expressing MDA-7/IL-24 (rPIV5-MDA7), rPIV5-V/P-CPI−；, rPIV5-CPI+, rPIV5-Rev, rPIV5-RL, rPIV5-P-S157A, rPIV5-P-S308A, rPIV5-L-A1981D, rPIV5-F-S443P, rPIV5-MDA7, rPIV5Δ；SH-CPI−；, or rPIV5Δ；SH-Rev. Also included are methods of making and using such oncolytic agents and compositions including such oncolytic agents.
