*5.3. Arming with Antiangiogenic Transgenes*

Angiogenesis is an important target of immunotherapies in clinical oncology. oAds have been armed with antiangiogenic mechanisms to enhance the antitumor effect of oncolysis. In human hepatocellular carcinoma (HCC) cells and in xenografts in mice, Li et al. showed anti-angiogenesis and antitumoral effects when endostatin was expressed by the E1B-55k deleted oAd CNHK200-mE [76]. Xiao and colleagues generated ZD55-VEGI-251, also an E1B55k-deleted oAd, armed with a secreted isoform of vascular endothelial cell growth inhibitor [77]. VEGI-251 inhibited angiogenesis in chick chorioallantoic membranes and suppressed tumor growth in xenograft models. Decorin, which is able to suppress multiple tyrosine kinase receptors including c-Met and the Wnt/β-catenin pathway, has also been employed. In a nude mice model of human prostate cancer, the decorin-expressing Ad.dcn reduced tumor burden, significantly inhibited skeletal metastases and improved survival [78]. The group of Chae-Ok Yun suppressed vascular endothelial growth factor (VEGF) by expressing VEGF-specific short-hairpin RNA (shRNA) or by expression of an artificial zinc-finger protein (F435-KOX) targeting the VEGF promoter [79,80].
