A non-replicating adenovirus 5 (Ad-5, El-deleted) encoding a human Fas-chimera (Fas-c) transgene under the control of a modified murine pre-proendothelin-1 (PPE-1) promoter, with potential anti-angiogenic activity. Upon the administration of ofranergene obadenovec, the modified murine PPE-1 promoter is specifically activated in PPE-1-expressing angiogenic endothelial cells residing in the tumor microvasculature. Subsequently, the Fas-c pro-apoptotic transgene, containing the human tumor necrosis factor (TNF) receptor 1 (TNFR-1/p55) and the signaling domain of Fas, is expressed in angiogenic endothelial cells. Fas-mediated apoptosis is activated via binding of the TNFR-1 receptor with TNF-alpha, which is more abundant in the tumor microenvironment (TME), enhancing specificity and limiting systemic toxicities.