Adenoviral-Mediated Transfer of the TNF-Related Apoptosis-Inducing Ligand/Apo-2 Ligand Gene Induces Tumor Cell Apoptosis

• Published in: The Journal of immunology (1950) Vol. 165; no. 5; pp. 2886 - 2894
• Main Authors: Griffith, Thomas S, Anderson, Richard D, Davidson, Beverly L, Williams, Richard D, Ratliff, Timothy L
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.09.2000
• Subjects: adenovirus; Adenoviruses, Human - drug effects; Adenoviruses, Human - genetics; Adenoviruses, Human - immunology; APO2L protein; Apoptosis - drug effects; Apoptosis - genetics; Apoptosis - immunology; Apoptosis Regulatory Proteins; Breast Neoplasms; Brefeldin A - pharmacology; caspase-8; Cell Death - drug effects; Cell Death - genetics; Cell Death - immunology; Cell Line; Cytotoxicity Tests, Immunologic; Disease Susceptibility; fas Receptor - immunology; fas Receptor - metabolism; Gene Transfer Techniques; Genetic Vectors - administration & dosage; Genetic Vectors - chemical synthesis; Genetic Vectors - immunology; Humans; Immunoglobulin Fc Fragments - pharmacology; Ligands; Male; Melanoma; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Membrane Glycoproteins - pharmacology; Prostatic Neoplasms; TNF-Related Apoptosis-Inducing Ligand; TRAIL protein; Tumor Cells, Cultured - immunology; Tumor Cells, Cultured - pathology; Tumor Cells, Cultured - virology; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - pharmacology; Urinary Bladder Neoplasms
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.165.5.2886

TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily 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 leads to the rapid production and expression of TRAIL protein, and subsequent death of the tumor cells. Tumor cell death was mediated by an apoptotic mechanism, as evidenced by the activation of caspase-8, cleavage of poly(ADP-ribose) polymerase, binding of annexin V, and inhibition by caspase inhibitor zVAD-fmk. These results define a novel method of using TRAIL as an antitumor therapeutic, and suggest the potential use for an adenovirus-encoding TRAIL as a method of gene therapy for numerous cancer types in vivo.