ZD55-TRAIL-IETD-Smac

**ZD55-TRAIL-IETD-Smac** is an experimental cancer-targeting dual-gene virotherapy based on the tumor-selective oncolytic adenoviral vector ZD55, which lacks the adenoviral E1B 55-kDa gene. The vector encodes a single TRAIL-IETD-Smac fusion transgene: the IETD sequence is a caspase-8-cleavable linker that enables generation of functional TRAIL and Smac effectors following apoptosis-pathway activation. TRAIL promotes extrinsic apoptosis through death receptors, while Smac relieves inhibitor-of-apoptosis-protein-mediated suppression of caspases, producing complementary proapoptotic activity. Preclinical studies reported complete eradication of hepatoma xenografts and enhanced activity with SNS-032 in pancreatic cancer models. ([europepmc.org](https://europepmc.org/article/PMC/3440030))