Systemically delivered Bacteroides thetaiotaomicron-derived bacterial extracellular vesicles inhibit primary and metastatic melanoma growth
5 affiliations
- 1Food, Microbiome and Health Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, United Kingdom
- 2Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA
- 3Microbes, Infection and Microbiomes, College of Medicine and Health, University of Birmingham, Birmingham, United Kingdom
- 4Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, United Kingdom
- 5School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, United Kingdom
Abstract
The gut microbiome can contribute to anti-tumor immunity and cancer therapy responses, but translating live microbe-based interventions remains challenging due to safety, controllability, and delivery constraints. Bacterial extracellular vesicles (BEVs) are an attractive cell-free alternative, as they package bacterial cargo into a nanoscale format capable of host-cell engagement, immunological activation, and systemic distribution. Here, we investigated the anti-tumor potential of BEVs derived from the human gut commensal Bacteroides thetaiotaomicron (Bt). We show that the delivery route is a major determinant of efficacy. Intravenous, but not intraperitoneal, administration produced robust anti-tumor activity in a B16F10 melanoma mouse model. Intravenously delivered Bt BEVs suppressed primary tumor growth in a dose-dependent manner and reduced metastatic outgrowth in the lung. Bt BEVs did not reduce B16F10 metabolic viability during a 24-h in vitro exposure, but they activated NF-κB and Toll-like receptor signaling in human reporter systems, and NanoLuc-associated signal from labeled BEV preparations was detected in excised tumor tissue following systemic administration. Although the host pathways responsible for tumor control remain to be defined, these findings identify naturally produced commensal-derived Bt BEVs as a candidate cell-free microbial therapeutic modality for cancer therapy.
IMPORTANCE: Gut bacteria can influence cancer immunity, but using live microorganisms as treatments creates practical and safety challenges. Bacterial extracellular vesicles offer a cell-free way to deliver microbial molecules to the host, yet the anti-cancer potential of vesicles naturally produced by common gut bacteria remains poorly defined. Here, we show that vesicles from the human gut bacterium Bacteroides thetaiotaomicron suppress primary melanoma growth and reduce lung tumor burden in mice when delivered intravenously, whereas delivery into the abdominal cavity is much less effective. The vesicle preparations did not reduce melanoma-cell viability directly in culture, suggesting that the in vivo effect is not explained by simple toxicity to tumor cells. These findings establish that naturally produced vesicles from a common gut bacterium can exert anti-tumor activity after systemic delivery and identify the administration route as an important determinant of their activity. These findings support their further evaluation as cell-free therapeutic platforms for cancer.
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BibTeX
@article{price2026systemically,
title = {{Systemically delivered Bacteroides thetaiotaomicron-derived bacterial extracellular vesicles inhibit primary and metastatic melanoma growth}},
author = {Christopher A. Price and Emily J. Jones and Nilda Ilker and Alicia D. Nicklin and Rokas Juodeikis and Alastair M. McKee and Luke J. Mitchell and Régis Stentz and Lindsay J. Hall and Simon R. Carding and Stephen D. Robinson},
journal = {Microbiology Spectrum},
year = {2026},
month = sep,
doi = {10.1128/spectrum.02512-26},
url = {https://doi.org/10.1128/spectrum.02512-26},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Systemically delivered Bacteroides thetaiotaomicron-derived bacterial extracellular vesicles inhibit primary and metastatic melanoma growth
AU - Christopher A. Price
AU - Emily J. Jones
AU - Nilda Ilker
AU - Alicia D. Nicklin
AU - Rokas Juodeikis
AU - Alastair M. McKee
AU - Luke J. Mitchell
AU - Régis Stentz
AU - Lindsay J. Hall
AU - Simon R. Carding
AU - Stephen D. Robinson
PY - 2026
DA - 2026/09/29
JO - Microbiology Spectrum
DO - 10.1128/spectrum.02512-26
UR - https://doi.org/10.1128/spectrum.02512-26
AB - The gut microbiome can contribute to anti-tumor immunity and cancer therapy responses, but translating live microbe-based interventions remains challenging due to safety, controllability, and delivery constraints. Bacterial extracellular vesicles (BEVs) are an attractive cell-free alternative, as they package bacterial cargo into a nanoscale format capable of host-cell engagement, immunological activation, and systemic distribution. Here, we investigated the anti-tumor potential of BEVs derived from the human gut commensal Bacteroides thetaiotaomicron (Bt). We show that the delivery route is a major determinant of efficacy. Intravenous, but not intraperitoneal, administration produced robust anti-tumor activity in a B16F10 melanoma mouse model. Intravenously delivered Bt BEVs suppressed primary tumor growth in a dose-dependent manner and reduced metastatic outgrowth in the lung. Bt BEVs did not reduce B16F10 metabolic viability during a 24-h in vitro exposure, but they activated NF-κB and Toll-like receptor signaling in human reporter systems, and NanoLuc-associated signal from labeled BEV preparations was detected in excised tumor tissue following systemic administration. Although the host pathways responsible for tumor control remain to be defined, these findings identify naturally produced commensal-derived Bt BEVs as a candidate cell-free microbial therapeutic modality for cancer therapy. IMPORTANCE: Gut bacteria can influence cancer immunity, but using live microorganisms as treatments creates practical and safety challenges. Bacterial extracellular vesicles offer a cell-free way to deliver microbial molecules to the host, yet the anti-cancer potential of vesicles naturally produced by common gut bacteria remains poorly defined. Here, we show that vesicles from the human gut bacterium Bacteroides thetaiotaomicron suppress primary melanoma growth and reduce lung tumor burden in mice when delivered intravenously, whereas delivery into the abdominal cavity is much less effective. The vesicle preparations did not reduce melanoma-cell viability directly in culture, suggesting that the in vivo effect is not explained by simple toxicity to tumor cells. These findings establish that naturally produced vesicles from a common gut bacterium can exert anti-tumor activity after systemic delivery and identify the administration route as an important determinant of their activity. These findings support their further evaluation as cell-free therapeutic platforms for cancer.
SN - 2165-0497
ER -