Cell reports. Medicine · 2026
Dual-system engineered bacteria and dendritic cells enable precise intratumoral IL-12 delivery and potent antitumor immunity.
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Deng Yuan, Liang Heng, Wan Arabella H, Liu Chuwei, Yan Shijia, Li Jiarui, Xiao Min, Zhou Qiusheng, Liu Ruonian, Zhang Zitong, Zhang Heteng, Cheng Huiya, Fu Chengyuan, Yao Qijun, Fang Juan, Neumann Silke, Wang Qiaoping, Huang Jun, Wang Zhi, Wan Guohui
Аннотация
Interleukin-12 (IL-12) potently stimulates antitumor immunity, but its clinical use is limited by systemic toxicity and poor spatial control. Here, we develop a dual-engineered delivery system that combines Escherichia coli Nissle 1917 (EcN) programmed for hypoxia- and quorum-sensing-regulated IL-12 expression with engineered dendritic cells (eDCs) that facilitate bacterial delivery and immune support. In murine colorectal cancer and liver metastasis models, eDC-EcN-IL12-QS preferentially localizes to tumors, increases intratumoral IL-12 and IFN- γ levels, enhances dendritic cell activation and CD8+ T cell infiltration, and suppresses tumor growth and metastatic burden. The system also prolongs survival and remains controllable by antibiotic-mediated clearance. These findings support a programmable microbial-cellular strategy for localized cytokine delivery and immune activation in immunologically cold tumors.