Adenoviral-mediated transfer of the TNF-related apoptosis-inducing ligand/apo-2 ligand gene induces tumor cell apoptosis

TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superf amily of cytokines that induces apoptosis in a variety of cancer cells. The results presented in this study demonstrate that introduction of the human TRAIL gene into TRAIL-sensitive tumor cells using an adenoviral vector lea ds to the rapid production and expression of TRAIL protein, and subsequent death Of the tumor cells. Tumor cell death was mediated by an apoptotic mec hanism, as evidenced by the activation of caspase-8, cleavage of poly(ADP-r ibose) polymerase, binding of annexin V, and inhibition by caspase inhibito r zVAD-fmk, These results define a novel method of using TRAIL as an antitu mor therapeutic, and suggest the potential use for an adenovirus-encoding T RAIL as a method of gene therapy for numerous cancer types in vivo.