Antitumor activity and prolonged expression from a TRAIL-expressing adenoviral vector.
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.
Lee
Jeongwu
J
Neuro-Oncology Branch, National Cancer Institute, National Institute of Neurologic Disorders and Stroke/NIH, 10 Center Drive, Bethesda, MD, USA.
Hampl
Monika
M
Albert
Paul
P
Fine
Howard A
HA
D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001201:Ascites; D001253:Astrocytes / Q000166:cytology; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D002051:Burkitt Lymphoma / Q000473:pathology; D002277:Carcinoma / Q000556:secondary / Q000628:therapy*; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000473:pathology; D018076:DNA, Complementary / Q000235:genetics; D003673:Defective Viruses / Q000235:genetics*; D004730:Endothelium, Vascular / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology; D015870:Gene Expression; D015723:Gene Library; D005813:Genes, Synthetic; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000627:therapeutic use*; D005909:Glioblastoma / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008819:Mice, Nude; D010534:Peritoneal Neoplasms / Q000556:secondary / Q000628:therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000502:physiology; D014471:Umbilical Veins; D023041:Xenograft Model Antitumor Assays
D051017:Apoptosis Regulatory Proteins; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha