ArticleJournal of virology2002
Hepatic DR5 induces apoptosis and limits adenovirus gene therapy product expression in the liver.
Article in Journal of virology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 36 citations in OpenAlex.
- Preclinical studies of a death receptor 5 fusion protein that ameliorates acute liver failure.Journal of molecular medicine (Berlin, Germany) · 2019Article
- Article
- Small molecule inhibitor YM155-mediated activation of death receptor 5 is crucial for chemotherapy-induced apoptosis in pancreatic carcinoma.Molecular cancer therapeutics · 2015Article
- Fas-mediated apoptotic signaling in the mouse brain following reovirus infection.Journal of virology · 2009Article
- Enhancement of cytotoxic T-lymphocyte response in aged mice by a novel treatment with recombinant AdIL-12 and wild-type adenovirus in rapid succession.Molecular therapy : the journal of the American Society of Gene Therapy · 2008Article
- Apoptosis of viral-infected airway epithelial cells limit viral production and is altered by corticosteroid exposure.Respiratory research · 2006Article
- Genetic heterogeneity and efficiency of two different methods of adenovirus-mediated gene transfer in a rat liver transplantation model.Surgery today · 2006Article
- Primary adenovirus-specific cytotoxic T lymphocyte response occurs after viral clearance and liver enzyme elevation.Gene therapy · 2005Article
- Defining strategies to extend duration of gene expression from targeted compacted DNA vectors.Gene therapy · 2004Article
- Transfection of IL-2 and/or IL-12 genes into spleen in treatment of rat liver cancer.World journal of gastroenterology · 2004Article
- Article
- CII-DC-AdTRAIL cell gene therapy inhibits infiltration of CII-reactive T cells and CII-induced arthritis.The Journal of clinical investigation · 2003Article
- Genetic heterogeneity in response to adenovirus gene therapy.BMC molecular biology · 2003Article
- Localization of TRAIL/TRAILR in fetal pancreas.World journal of gastroenterology · 2003Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
A major limitation of adenovirus (Ad) gene therapy product expression in the liver is subsequent elimination of the hepatocytes expressing the gene therapy product. This elimination is caused by both necrosis and apoptosis related to the innate and cell-mediated immune response to the Ad. Apoptosis of hepatocytes can be induced by the innate immune response by signaling through death domain receptors on hepatocytes including the tumor necrosis factor alpha (TNF-alpha) receptor (TNFR), Fas, and death domain receptors DR4 and DR5. We have previously shown that blocking signaling through TNFR enhances and prolongs gene therapy product expression in the liver. In the present study, we constructed an Ad that produces a soluble DR5-Fc (AdsDR5), which is capable of neutralizing TNF-related apoptosis-inducing ligand (TRAIL). AdsDR5 prevents TRAIL-mediated apoptosis of CD3-activated T cells and decreases hepatocyte apoptosis after AdCMVLacZ administration and enhances the level and duration of lacZ transgene expression in the liver. In addition to blocking TRAIL and directly inhibiting apoptosis, AdsDR5 decreases production of gamma interferon (IFN-gamma) and TNF-alpha and decreases NK cell activation, all of which limit Ad-mediated transgene expression in the liver. These results indicate that (i) AdsDR5 produces a DR5-Fc capable of neutralizing TRAIL, (ii) AdsDR5 can reduce activation of NK cells and reduce induction of IFN-gamma and TNF-alpha after Ad administration, and (iii) administration of AdsDR5 can enhance Ad gene therapy in the liver.
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Registered trials
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