ArticleCancer gene therapy2007
Membrane-localized activation of glucuronide prodrugs by beta-glucuronidase enzymes.
Article in Cancer gene therapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 48 citations in OpenAlex.
- Tumour-specific STING agonist synthesis via a two-component prodrug system.Nature chemistry · 2025Article
- Safe and Efficient Intracellular Release of SN38 via Lysosomal-Responsive SN38-G Loaded Liposomes.ACS applied bio materials · 2025Article
- Engineering CAR-T cells to activate small-molecule drugs in situ.Nature chemical biology · 2022Article
- Beta-Glucuronidase Catalyzes Deconjugation and Activation of Curcumin-Glucuronide in Bone.Journal of natural products · 2019Article
- Pharmacokinetic-pharmacodynamic correlations in the development of ginger extract as an anticancer agent.Scientific reports · 2018Article
- High-Affinity Ligands Can Trigger T Cell Receptor Signaling Without CD45 Segregation.Frontiers in immunology · 2018Article
- The Affinity of Elongated Membrane-Tethered Ligands Determines Potency of T Cell Receptor Triggering.Frontiers in immunology · 2017Article
- Modular assembly of synthetic proteins that span the plasma membrane in mammalian cells.BMC biotechnology · 2016Article
- Effect of Cellular Location of Human Carboxylesterase 2 on CPT-11 Hydrolysis and Anticancer Activity.PloS one · 2015Article
- Impediments to enhancement of CPT-11 anticancer activity by E. coli directed beta-glucuronidase therapy.PloS one · 2015Article
- Expression of β-glucuronidase on the surface of bacteria enhances activation of glucuronide prodrugs.Cancer gene therapy · 2013Article
- Article
- Substrate mediated enzyme prodrug therapy.PloS one · 2012Article
- Enhancement of CPT-11 antitumor activity by adenovirus-mediated expression of β-glucuronidase in tumors.Cancer gene therapy · 2011Article
- Tumor-targeting prodrug-activating bacteria for cancer therapy.Cancer gene therapy · 2008Article
- Gene expression imaging by enzymatic catalysis of a fluorescent probe via membrane-anchored beta-glucuronidase.Gene therapy · 2007Article
- Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene-mediated enzyme prodrug therapy (GDEPT) seeks to increase the therapeutic index of anti-neoplastic agents by promoting selective activation of relatively nontoxic drug derivatives at sites of specific enzyme expression. Glucuronide prodrugs are attractive for GDEPT due to their low toxicity, bystander effect in the interstitial tumor space and the large range of possible glucuronide drug targets. In this study, we expressed human, murine and Esherichia coli beta-glucuronidase on tumor cells and examined their in vitro and in vivo efficacy for the activation of glucuronide prodrugs of 9-aminocamptothecin and p-hydroxy aniline mustard. We show that (1) fusion of beta-glucuronidase to the Ig-like C(2)-type and Ig-hinge-like domains of the B7-1 antigen followed by the B7-1 transmembrane domain anchored high levels of active murine and human beta-glucuronidase on cells, (2) strong bystander killing of tumor cells was achieved in vitro by murine beta-glucuronidase activation of prodrug, (3) potent in vivo anti-tumor activity was achieved by prodrug treatment of tumors that expressed murine beta-glucuronidase and (4) the p-hydroxy aniline prodrug was more effective in vivo than the 9-aminocamptothecin prodrug. Our results demonstrate that surface expression of murine beta-glucuronidase for activation of a glucuronide prodrug of p-hydroxy aniline mustard may be useful for more selective therapy of cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.