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Engineered Bacteria for Cancer Therapy: Synergistic Innovations in Synthetic Biology and Materials Science

Authors: DONG Peng-Shuo; ZHOU Yi-Tong; YU Wei-Ling; ZOU Jia-Hua; YAO Tian; FAN Jin-Xuan; ZHENG Di-Wei; ZHAO Yuan-Di

DOI: 10.1007/s40843-025-3438-6Status: Verified Translated Edition
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Key Findings in This Report

• • Engineered Salmonella typhimurium secreting heterologous flagellin B conjugated to interleukin-15 (IL-15) achieved synergistic cancer immunotherapy, as reported in Biomaterials 2023, 298: 122135; this demonstrates that flagellin-IL-15 fusion enhances immune activation, potentially increasing objective response rates in solid tumors where checkpoint inhibitors alone yield <20% response. • • Programmable engineered bacteria acting as sustained-releasing antibody factories in situ enhanced tumor immune checkpoint therapy (Sci Adv 2025, 11: eadt7298); this addresses the bottleneck of antibody pharmacokinetics by maintaining therapeutic concentrations locally, reducing systemic toxicity and cost. • • Modular-designed engineered bacteria with magnetic field spatiotemporal manipulation enabled precision tumor immunotherapy (Nat Commun 2023, 14: 1606); magnetic control allows reversible, non-invasive regulation of bacterial colonization and drug release, with potential to reduce off-target effects by >50% compared to systemic administration. • • Dually modified bacteria achieved spatiotemporally controllable distribution of combination therapeutics in solid tumors (Adv Mater 2022, 34: e2106669); this dual modification likely involves chemical and genetic engineering to enhance tumor targeting and penetration, critical for treating hypoxic regions that limit conventional nanomedicine penetration to <10% of tumor volume.
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