Dual-system engineered bacteria and dendritic cells enable precise intratumoral IL-12 delivery and potent antitumor immunity.
basic_science · Level V
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- Record sourced from PubMed, PMID 42105768.
- Also identified by DOI 10.1016/j.xcrm.2026.102801.
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Abstract
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<sup>+</sup> 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.