ArticleJournal of controlled release : official journal of the Controlled Release Society2015
Trg-deficient Salmonella colonize quiescent tumor regions by exclusively penetrating or proliferating.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Synthetic biology of oncolytic bacteria: Comparative microbial chassis and precise killing strategies.Toxicology reports · 2026Review
- Peripheral blood CXCL1 serves as a non-invasive dynamic biomarker for intratumoral colonization of attenuated Salmonella.Biomarker research · 2026Article
- Spatial Heterogeneity of Intratumoral Microbiota and Its Roles in Tumor-Microbiota Interactions and Therapeutic Implications.Pathogens (Basel, Switzerland) · 2026Review
- Engineering oncolytic bacteria as precision cancer therapeutics: design principles, therapeutic strategies, and translational perspectives.Protein & cell · 2026Review
- Intratumoral microbiota and metabolites: dual roles in cancer progression and therapeutic opportunities.Cell communication and signaling : CCS · 2026Review
- Molecular mechanisms of bacteria-mediated cancer immunotherapy: from intratumoral microbiota to engineered therapeutics.Frontiers in immunology · 2026Review
- Controlling intracellular protein delivery, tumor colonization and tissue distribution using flhDC in clinically relevant ΔsseJ Salmonella.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Precision tumor treatment utilizing bacteria: principles and future perspectives.Applied microbiology and biotechnology · 2025Review
- Salmonella-based therapeutic strategies: improving tumor microenvironment and bringing new hope for cancer immunotherapy.Medical oncology (Northwood, London, England) · 2024Review
- Flagellate bacteria-mediated tumour antigen delivery: A novel approach to enhance dendritic cell activation for in situ cancer vaccination.Microbial biotechnology · 2024Review
- Review
- Neutrophil-Mediated Tumor-Targeting Delivery System of Oncolytic Bacteria Combined with ICB for Melanoma Lung Metastasis Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Bacterial delivery of therapeutic proteins to the nuclei of cancer cells.Biotechnology and bioengineering · 2023Article
- Review
- Bioengineered Escherichia coli Nissle 1917 for tumour-targeting therapy.Microbial biotechnology · 2020Review
- Bacteria-cancer interactions: bacteria-based cancer therapy.Experimental & molecular medicine · 2019Review
- Review
- The motility regulator flhDC drives intracellular accumulation and tumor colonization of Salmonella.Journal for immunotherapy of cancer · 2019Article
- Endostatin gene therapy delivered by attenuated Salmonella typhimurium in murine tumor models.Cancer gene therapy · 2018Article
- Solid tumors provide niche-specific conditions that lead to preferential growth of Salmonella.Oncotarget · 2016Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
Chemotherapeutics fail to effectively treat tumors because they cannot reach quiescent regions far from blood vessels. Motile Salmonella are an attractive delivery system that could break this therapeutic barrier. However, little is known about the dissemination and tissue penetration of individual bacteria in tumors after intravenous administration. We hypothesized that eliminating the Trg receptor would improve accumulation in tumor quiescence. To test this hypothesis, we deleted the trg gene from nonpathogenic Salmonella. To quantify individual bacterial behavior, we measured tissue penetration in a tumor-on-a-chip device and measured colony localization in mouse tumors using immunofluorescence. In tumors in vitro and in mice, trg(-) Salmonella penetrated farther into tissue than control bacteria. This difference in localization was caused by the inability to sense sugars in well perfused tissue. Three distinct bacterial phenotypes were observed: proliferating, penetrating, and inactive. Large proliferating colonies, containing more than 40% of individual bacteria, only formed less than 60μm from blood vessels. Small colonies, in comparison, were present both near (inactive) and far (penetrating) from vessels. The farthest was 361.2μm from a vessel, demonstrating the ability to target avascular regions. In addition, colonization was most pronounced in poorly vascularized tumor regions. We show that deletion of trg amplifies Salmonella accumulation in quiescent tumor regions, and, for the first time, identify biological processes that control bacterial distribution in tumors. Understanding how Salmonella penetrate tissue, target quiescence and specifically replicate in tumors are essential steps toward creating a tightly controlled, tunable bacterial therapy.
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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.