ArticleCancer research2008
Optimized clostridium-directed enzyme prodrug therapy improves the antitumor activity of the novel DNA cross-linking agent PR-104.
Article in Cancer research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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.
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Who cites it
27 citing papers in PubMed, 62 citations in OpenAlex.
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- Engineered Bacteria-Nano Hybrid System: The Intelligent Drug Factory for Next-Generation Cancer Immunotherapy.Pharmaceutics · 2025Review
- Anti-Cancer Strategies Using Anaerobic Spore-Forming BacteriaLife (Basel, Switzerland) · 2025Review
- Tumor-targeting bacteria as immune stimulants - the future of cancer immunotherapy?Critical reviews in microbiology · 2024Review
- Microbial Therapeutics in Oncology: A Comprehensive Review of Bacterial Role in Cancer Treatment.Cureus · 2024Review
- Clostridium Bacteria: Harnessing Tumour Necrosis for Targeted Gene Delivery.Molecular diagnosis & therapy · 2024Article
- Design and Biological Evaluation of Piperazine-Bearing Nitrobenzamide Hypoxia/GDEPT Prodrugs: The Discovery of CP-506.ACS medicinal chemistry letters · 2023Article
- Use of an optimised enzyme/prodrug combination for Clostridia directed enzyme prodrug therapy induces a significant growth delay in necrotic tumours.Cancer gene therapy · 2022Article
- Interrogation of the Structure-Activity Relationship of a Lipophilic Nitroaromatic Prodrug Series Designed for Cancer Gene Therapy Applications.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Article
- An obligatory anaerobicOncology letters · 2018Article
- Review
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- Bacteria in Cancer Therapy: Renaissance of an Old Concept.International journal of microbiology · 2016Review
- Obligate anaerobicOncology letters · 2015Article
- Clostridium to treat cancer: dream or reality?Annals of translational medicine · 2015Article
- Impediments to enhancement of CPT-11 anticancer activity by E. coli directed beta-glucuronidase therapy.PloS one · 2015Article
- Genome sequence of Clostridium sporogenes DSM 795(T), an amino acid-degrading, nontoxic surrogate of neurotoxin-producing Clostridium botulinum.Standards in genomic sciences · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
We have previously shown that spores of the nonpathogenic clostridial strain C. sporogenes genetically engineered to express the E. coli-derived cytosine deaminase gene are effective in converting systemically injected nontoxic 5-fluorocytosine into the toxic anticancer drug 5-fluorouracil, thereby producing tumor-specific antitumor activity. To improve the expression of E. coli-derived genes with this system, we first replaced the original fdP promoter in the vector with one of two powerful endogenous clostridial promoters: that of the thiolase gene (thlP) and that for the clostridial transcription factor abrB310 (abrBP). These substitutions improved protein expression levels of the prodrug-activating genes by 2- to 3-fold in comparison with fdP-driven expression. However, despite these strong promoters, we found much higher expression of the nitroreductase (NTR) protein in the E. coli host compared with the clostridial host, which we hypothesized could be the result of different codon use between the two organisms. To test this, we constructed new expression vectors with an artificially synthesized NTR gene using optimized clostridial codons (sNTR). Results from both enzymatic assays and Western blots of cell extracts from clostridial transformants harboring plasmid constructs of thlP-sNTR and abrBP-sNTR showed that the expression and activity of the NTR gene product was increased by approximately 20-fold compared with the original construct. In vivo studies with i.v. administered sNTR-expressing C. sporogenes spores in SiHa tumor-bearing mice showed significantly improved antitumor efficacy when combined with either 5-aziridinyl-2,4-dinitrobenzamide (CB1954) or the novel dinitrobenzamide mustard prodrug, PR-104.
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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.