The tumor microenvironment plays an important role in tumor growth and progression. Here we demonstrate that vaccinia virus-mediated， constitutively expressed intratumoral antibodies against vascular endothelial growth factor (VEGF)， epidermal growth factor receptor (EGFR)， and fibroblast activation protein (FAP) significantly improved tumor regression and oncolytic virotherapy through suppression of angiogenesis， cell proliferation， and stromagenesis in virus-colonized tumors. In contrast to the tumor growth inhibition by the three tumor growth-inhibiting antibodies individually， when two of the three antibodies were expressed simultaneously by single vaccinia virus strains tumor regression was further enhanced. These findings strongly indicate that interference with the two tumor growth-stimulating mechanisms did in fact result in enhanced therapeutic efficacy in tumor xenograft models and may lead to an effective therapy in patients with cancer.