Antitumor activity and prolonged expression from a TRAIL-expressing adenoviral vector

Neoplasia. Jul-Aug 2002;4(4):312-23. doi: 10.1038/sj.neo.7900245.

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a variety of transformed cell lines, but generally spares most normal cells. Transduction by an adenoviral vector expressing human TRAIL cDNA (Ad.TRAIL-GFP) resulted in both direct tumor cell killing as well as a potent bystander effect through presentation of TRAIL by transduced normal cells. Administration of Ad.TRAIL-GFP significantly prolonged survival of mice harboring either intracerebral glioblastomas or breast carcinoma-induced peritoneal carcinomatosis. Additionally, TRAIL induced prolonged transgene expression in normal tissue, presumably as a result of diminished immune-mediated destruction of vector-transduced cells. Taken together, these data suggest that vector-mediated transduction of TRAIL may represent an effective strategy for cancer gene therapy.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviruses, Human / genetics*
  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Ascites
  • Astrocytes / cytology
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • Burkitt Lymphoma / pathology
  • Carcinoma / secondary
  • Carcinoma / therapy*
  • Cells, Cultured
  • Colonic Neoplasms / pathology
  • DNA, Complementary / genetics
  • Defective Viruses / genetics*
  • Endothelium, Vascular / cytology
  • Fibroblasts / cytology
  • Gene Expression
  • Gene Library
  • Genes, Synthetic
  • Genetic Therapy*
  • Genetic Vectors / therapeutic use*
  • Glioblastoma / pathology
  • Glioblastoma / therapy*
  • Humans
  • Male
  • Mammary Neoplasms, Experimental / pathology
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / physiology
  • Mice
  • Mice, Nude
  • Peritoneal Neoplasms / secondary
  • Peritoneal Neoplasms / therapy*
  • Reverse Transcriptase Polymerase Chain Reaction
  • TNF-Related Apoptosis-Inducing Ligand
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / physiology
  • Umbilical Veins
  • Xenograft Model Antitumor Assays

Substances

  • Apoptosis Regulatory Proteins
  • DNA, Complementary
  • Membrane Glycoproteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tnfsf10 protein, mouse
  • Tumor Necrosis Factor-alpha