Anaerobic bacteria can accumulate and proliferate within hypoxic and necrotic regions of solid tumours, stimulating inflammation and triggering an antitumour immune response. Zheng et al. have engineered an attenuated strain of Salmonella typhimurium to overexpress and secrete a heterologous bacterial flagellin (FlaB), which is a ligand for Toll-like receptor 5 (TLR5). In tumour-bearing mice, the engineered FlaB-secreting bacteria effectively and safely suppressed tumour growth and metastasis, and prolonged survival through the activation of TLR4 and TLR5 signalling pathways in host immune cells.
References
Zheng, J. H. et al. Two-step enhanced cancer immunotherapy with engineered Salmonella typhimurium secreting heterologous flagellin. Sci. Transl Med. 9, eaak9537 (2017)
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Crunkhorn, S. Bacterium-based immunotherapy. Nat Rev Drug Discov 16, 240 (2017). https://doi.org/10.1038/nrd.2017.54
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DOI: https://doi.org/10.1038/nrd.2017.54