ArticleBritish journal of cancer2002
Secreted and tumour targeted human carboxylesterase for activation of irinotecan.
Article in British journal of cancer, 2002. 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, 40 citations in OpenAlex.
- Phytochemicals and Cancer Treatment: Cell-Derived and Biomimetic Vesicles as Promising Carriers.Pharmaceutics · 2023Review
- Engineering CAR-T cells to activate small-molecule drugs in situ.Nature chemical biology · 2022Article
- Optimization of a Neural Stem-Cell-Mediated Carboxylesterase/Irinotecan Gene Therapy for Metastatic Neuroblastoma.Molecular therapy oncolytics · 2017Article
- Enzyme/Prodrug Systems for Cancer Gene Therapy.Current pharmacology reports · 2016Article
- Effect of Cellular Location of Human Carboxylesterase 2 on CPT-11 Hydrolysis and Anticancer Activity.PloS one · 2015Article
- Effects of genetically engineered stem cells expressing cytosine deaminase and interferon-beta or carboxyl esterase on the growth of LNCaP rrostate cancer cells.International journal of molecular sciences · 2012Article
- A cell-delivered and cell-activated SN38-dextran prodrug increases survival in a murine disseminated pancreatic cancer model.Small (Weinheim an der Bergstrasse, Germany) · 2012Article
- The feasibility of enzyme targeted activation for amino acid/dipeptide monoester prodrugs of floxuridine; cathepsin D as a potential targeted enzyme.Molecules (Basel, Switzerland) · 2012Article
- A self-contained enzyme activating prodrug cytotherapy for preclinical melanoma.Molecular biology reports · 2012Article
- Polymer micelles with hydrazone-ester dual linkers for tunable release of dexamethasone.Pharmaceutical research · 2011Article
- Modifications of human carboxylesterase for improved prodrug activation.Expert opinion on drug metabolism & toxicology · 2008Review
- An improved human carboxylesterase for enzyme/prodrug therapy with CPT-11.Cancer gene therapy · 2008Article
- Tumor targeting carboxylesterase fused with anti-CEA scFv improve the anticancer effect with a less toxic dose of irinotecan.Cancer gene therapy · 2008Article
- Review
- Gene-directed enzyme prodrug therapy with carboxylesterase enhances the anticancer efficacy of the conditionally replicating adenovirus AdDelta24.Gene therapy · 2005Article
- Adenoviral vector-mediated expression of a gene encoding secreted, EpCAM-targeted carboxylesterase-2 sensitises colon cancer spheroids to CPT-11.British journal of cancer · 2005Article
- Triacylglycerol hydrolase is localized to the endoplasmic reticulum by an unusual retrieval sequence where it participates in VLDL assembly without utilizing VLDL lipids as substrates.Molecular biology of the cell · 2005Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Irinotecan (CPT-11) is an anticancer agent for the treatment of colon cancer. CPT-11 can be considered as a prodrug, since it needs to be activated into the toxic drug SN-38 by the enzyme carboxylesterase. An approach to achieve tumour specific activation of CPT-11 is to transduce the cDNA encoding carboxylesterase into tumour cells. A secreted form of carboxylesterase may diffuse through a tumour mass and may activate CPT-11 extracellularly. This could enhance the antitumour efficacy by exerting a bystander effect on untransduced cells. In addition a secreted tumour-targeted form of carboxylesterase should prevent leakage of the enzyme from the site of the tumour into the circulation. We have constructed a secreted form of human liver carboxylesterase-2 by deletion of the cellular retention signal and by cloning the cDNA downstream of an Ig kappa leader sequence. The protein was secreted by transfected cells and showed both enzyme activity and efficient CPT-11 activation. To obtain a secreted, tumour-targeted form of carboxylesterase-2 the cDNA encoding the human scFv antibody C28 directed against the epithelial cell adhesion molecule EpCAM, was inserted between the leader sequence and carboxylesterase-2. This fusion protein showed CPT-11 activation and specific binding to EpCAM expressing cells. Importantly, in combination with CPT-11 both recombinant carboxylesterase proteins exerted strong antiproliferative effects on human colon cancer cells. They are, therefore, promising new tools for gene directed enzyme prodrug therapy approaches for the treatment of colon carcinoma with CPT-11.
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