ArticleCancer gene therapy2008
An improved human carboxylesterase for enzyme/prodrug therapy with CPT-11.
Article in Cancer gene therapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 52 citations in OpenAlex.
- Engineered adult stem cells: a promising tool for anti-cancer therapy.BMB reports · 2023Review
- Stem cells for the treatment of glioblastoma: a 20-year perspective.CNS oncology · 2021Review
- GMP Production and Scale-Up of Adherent Neural Stem Cells with a Quantum Cell Expansion System.Molecular therapy. Methods & clinical development · 2018Article
- Article
- Human Neural Stem Cell Biodistribution and Predicted Tumor Coverage by a Diffusible Therapeutic in a Mouse Glioma Model.Stem cells translational medicine · 2017Article
- Optimization of a Neural Stem-Cell-Mediated Carboxylesterase/Irinotecan Gene Therapy for Metastatic Neuroblastoma.Molecular therapy oncolytics · 2017Article
- Selective Inhibitors of Human Liver Carboxylesterase Based on a β-Lapachone Scaffold: Novel Reagents for Reaction Profiling.Journal of medicinal chemistry · 2017Article
- Enzyme/Prodrug Systems for Cancer Gene Therapy.Current pharmacology reports · 2016Article
- Carboxylesterases: General detoxifying enzymes.Chemico-biological interactions · 2016Review
- Challenges and Opportunities with Non-CYP Enzymes Aldehyde Oxidase, Carboxylesterase, and UDP-Glucuronosyltransferase: Focus on Reaction Phenotyping and Prediction of Human Clearance.The AAPS journal · 2016Review
- Tumour-selective targeting of drug metabolizing enzymes to treat metastatic cancer.British journal of pharmacology · 2016Review
- L-MYC Expression Maintains Self-Renewal and Prolongs Multipotency of Primary Human Neural Stem Cells.Stem cell reports · 2016Article
- Effect of Cellular Location of Human Carboxylesterase 2 on CPT-11 Hydrolysis and Anticancer Activity.PloS one · 2015Article
- Co-treatment with therapeutic neural stem cells expressing carboxyl esterase and CPT-11 inhibit growth of primary and metastatic lung cancers in mice.Oncotarget · 2014Article
- Neural stem cell-mediated delivery of irinotecan-activating carboxylesterases to glioma: implications for clinical use.Stem cells translational medicine · 2013Article
- Magnetic resonance imaging tracking of ferumoxytol-labeled human neural stem cells: studies leading to clinical use.Stem cells translational medicine · 2013Article
- Modulation of esterified drug metabolism by tanshinones from Salvia miltiorrhiza ("Danshen").Journal of natural products · 2013Article
- 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
- Global and local molecular dynamics of a bacterial carboxylesterase provide insight into its catalytic mechanism.Journal of molecular modeling · 2012Article
- Therapeutic targeting of subdural medulloblastomas using human neural stem cells expressing carboxylesterase.Cancer gene therapy · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
CPT-11 is a potent antitumor agent that is activated by carboxylesterases (CE) and intracellular expression of CEs that can activate the drug results in increased cytotoxicity to the drug. As activation of CPT-11 (irinotecan-7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin) by human CEs is relatively inefficient, we have developed enzyme/prodrug therapy approaches based on the CE/CPT-11 combination using a rabbit liver CE (rCE). However, the in vivo application of this technology may be hampered by the development of an immune response to rCE. Therefore, we have developed a mutant human CE (hCE1m6), based on the human liver CE hCE1, that can activate CPT-11 approximately 70-fold more efficiently than the wild-type protein and can be expressed at high levels in mammalian cells. Indeed, adenoviral-mediated delivery of hCE1m6 with human tumor cells resulted in up to a 670-fold reduction in the IC(50) value for CPT-11, as compared to cells transduced with vector control virus. Furthermore, xenograft studies with human tumors expressing hCE1m6 confirm the ability of this enzyme to activate CPT-11 in vivo and induce antitumor activity. We propose that this enzyme should likely be less immunogenic than rCE and would be suitable for the in vivo application of CE/CPT-11 enzyme/prodrug therapy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.