Abstract: New recombinant oncolytic viral vectors have been constructed based on a known herpes simplex virus-1 with a single 34.5 gene and a synctial mutation (called OncSyn (OS) virus), which was designed to be more immunogenic than the parental OS virus largely due to deletion of the viral gene viral host shutoff (vhs) gene (the “OSV” virus). In another embodiment, the OSV virus was constructed to constitutively express 15-PGDH (the “OSVP” virus), the principal enzyme responsible for degradation of PGE2. OSVP was shown to decrease both breast tumors and prostate cancer tumors in mice models. In addition, OSVP was shown to trigger substantial inflammatory cytokine production and pro mote anti-tumor immune responsiveness. These altered viruses, OSV and OSVP, can be used to treat various cancers including breast, prostate, liver, colon, and other tissues. Other exogenous genes can be added to either OSV or OSVP to improve the therapeutic response.