ArticleCancer gene therapy2022
Use of an optimised enzyme/prodrug combination for Clostridia directed enzyme prodrug therapy induces a significant growth delay in necrotic tumours.
Article in Cancer gene therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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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
12 citing papers in PubMed.
- Review
- Engineering bacteria for enhanced tumor therapy: from surface modification to synthetic genetic circuits.Journal of hematology & oncology · 2025Review
- Strategies for engineering domesticated and undomesticated human microbes.Current opinion in biotechnology · 2025Review
- Designing live bacterial therapeutics for cancer.Advanced drug delivery reviews · 2025Review
- Anti-Cancer Strategies Using Anaerobic Spore-Forming BacteriaLife (Basel, Switzerland) · 2025Review
- Gut microbiota and metabolites associated with immunotherapy efficacy in extensive-stage small cell lung cancer: a pilot study.Journal of thoracic disease · 2024Article
- Multiplex genetic manipulations in Clostridium butyricum and Clostridium sporogenes to secrete recombinant antigen proteins for oral-spore vaccination.Microbial cell factories · 2024Article
- Clostridium Bacteria: Harnessing Tumour Necrosis for Targeted Gene Delivery.Molecular diagnosis & therapy · 2024Article
- Structure of gut microbiota and characteristics of fecal metabolites in patients with lung cancer.Frontiers in cellular and infection microbiology · 2023Article
- Heterologous Gene Regulation in Clostridia: Rationally Designed Gene Regulation for Industrial and Medical Applications.ACS synthetic biology · 2022Article
- Engineered bacteria as drug delivery vehicles: Principles and prospects.Engineering microbiology · 2022Review
- Efficient Secretion of Murine IL-2 From an Attenuated Strain ofFrontiers in microbiology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
Abstract
Necrosis is a typical histological feature of solid tumours that provides a selective environment for growth of the non-pathogenic anaerobic bacterium Clostridium sporogenes. Modest anti-tumour activity as a single agent encouraged the use of C. sporogenes as a vector to express therapeutic genes selectively in tumour tissue, a concept termed Clostridium Directed Enzyme Prodrug Therapy (CDEPT). Here, we examine the ability of a recently identified Neisseria meningitidis type I nitroreductase (NmeNTR) to metabolise the prodrug PR-104A in an in vivo model of CDEPT. Human HCT116 colon cancer cells stably over-expressing NmeNTR demonstrated significant sensitivity to PR-104A, the imaging agent EF5, and several nitro(hetero)cyclic anti-infective compounds. Chemical induction of necrosis in human H1299 xenografts by the vascular disrupting agent vadimezan promoted colonisation by NmeNTR-expressing C. sporogenes, and efficacy studies demonstrated moderate but significant anti-tumour activity of spores when compared to untreated controls. Inclusion of the pre-prodrug PR-104 into the treatment schedule provided significant additional activity, indicating proof-of-principle. Successful preclinical evaluation of a transferable gene that enables metabolism of both PET imaging agents (for vector visualisation) and prodrugs (for conditional enhancement of efficacy) is an important step towards the prospect of CDEPT entering clinical evaluation.
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Identifiers
33558701What 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.