ArticleGene therapy2009
Bacterial delivery of a novel cytolysin to hypoxic areas of solid tumors.
Article in Gene therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 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
90 citing papers in PubMed, 188 citations in OpenAlex.
- Bacterial-based cancer therapy: mechanisms and therapeutic advances.Molecular biomedicine · 2026Review
- In vitro and in vivo antitumor activity of Laz-expressing Salmonella Typhimurium YB1 via optimized secretion and regulation.AMB Express · 2026Article
- Engineering oncolytic bacteria as precision cancer therapeutics: design principles, therapeutic strategies, and translational perspectives.Protein & cell · 2026Review
- Molecular mechanisms of bacteria-mediated cancer immunotherapy: from intratumoral microbiota to engineered therapeutics.Frontiers in immunology · 2026Review
- The renaissance ofFrontiers in immunology · 2026Review
- Tigecycline suppresses colon cancer stem cells and impairs tumor engraftment by targeting SNAI1-regulated epithelial-mesenchymal transition.Acta pharmacologica Sinica · 2026Article
- Self-Adjusting Engineered Probiotic for Targeted Tumor Colonization and Local Therapeutics Delivery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Designing live bacterial therapeutics for cancer.Advanced drug delivery reviews · 2025Review
- Expression of Fluorescence Reporters and Natural Products in Native GutACS synthetic biology · 2025Article
- Precision tumor treatment utilizing bacteria: principles and future perspectives.Applied microbiology and biotechnology · 2025Review
- Ultrasound spatiotemporally enables prolonged therapeutic mRNA translation in engineered bacteria for enhanced cancer immunotherapy.Theranostics · 2025Article
- Engineered Bacteria for Disease Diagnosis and Treatment Using Synthetic Biology.Microbial biotechnology · 2025Review
- Reprogramming the tumor immune microenvironment using engineered dual-drug loaded Salmonella.Nature communications · 2024Article
- Exploiting bacteria for cancer immunotherapy.Nature reviews. Clinical oncology · 2024Review
- AI-2 quorum sensing controlled delivery of cytolysin-A by tryptophan auxotrophic low-endotoxic Salmonella and its anticancer effects in CT26 mice with colon cancer.Journal of advanced research · 2024Article
- Insights into the enigma of oral streptococci in carcinogenesis.Microbiology and molecular biology reviews : MMBR · 2024Review
- Overcoming the nutritional immunity by engineering iron-scavenging bacteria for cancer therapy.eLife · 2024Article
- Promising dawn in tumor microenvironment therapy: engineering oral bacteria.International journal of oral science · 2024Review
- Enhancing tumor-specific recognition of programmable synthetic bacterial consortium for precision therapy of colorectal cancer.NPJ biofilms and microbiomes · 2024Article
- Dynamic Gene Expression Mitigates Mutational Escape in Lysis-Driven Bacteria Cancer Therapy.Biodesign research · 2024Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The efficacy of current anti-cancer gene therapies is limited by the inability of gene vectors to penetrate the poorly vascularized, hypoxic regions of tumors, leaving these sites untreated. We describe a new approach for targeting gene therapy to these sites, which employs an attenuated strain of the non-pathogenic bacterium, Salmonella typhimurium, carrying an exogenous (that is, reporter or therapeutic) gene under the regulation of a new, highly hypoxia-inducible promoter (FF+20(*)). This bacterial vector was seen to rapidly migrate into, and thrive in, hypoxic areas of both mammary tumor spheroids grown in vitro and orthotopic mammary tumors after systemic injection. Using the reporter gene construct, FF+20(*)-lacZ, we show that bacterial expression of high levels of beta-galactosidase occurred only in hypoxic/necrotic sites of spheroids and tumors. We then replaced the reporter gene with one encoding a novel cytotoxic protein (HlyE) and showed that this was also expressed by bacteria only in hypoxic regions of murine mammary tumors. This resulted in a marked increase in tumor necrosis and reduced tumor growth. Our system represents a promising new strategy for delivering gene therapy to poorly vascularized regions of tumors and shows, for the first time, the efficacy of HlyE as an anti-tumor agent.
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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.