Dual-system engineered bacteria and dendritic cells enable precise intratumoral IL-12 delivery and potent antitumor immunity

  • Cell Rep Med. 2026 Jun 16;7(6):102801. doi: 10.1016/j.xcrm.2026.102801.
Yuan Deng  1 ,  Heng Liang  1 ,  Arabella H Wan  2 ,  Chuwei Liu  2 ,  Shijia Yan  1 ,  Jiarui Li  1 ,  Min Xiao  1 ,  Qiusheng Zhou  1 ,  Ruonian Liu  1 ,  Zitong Zhang  1 ,  Heteng Zhang  1 ,  Huiya Cheng  1 ,  Chengyuan Fu  1 ,  Qijun Yao  3 ,  Juan Fang  4 ,  Silke Neumann  5 ,  Qiaoping Wang  6 ,  Jun Huang  7 ,  Zhi Wang  8 ,  Guohui Wan  9
Affiliations
  • 1. State Key Laboratory of Anti-Infective Drug Discovery and Development, National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
  • 2. Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
  • 3. Department of General Surgery (Colorectal Surgery), Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China.
  • 4. Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou 510055, China.
  • 5. Department of Pathology, Otago Medical School, University of Otago, Dunedin 9016, New Zealand.
  • 6. Laboratory of Metabolism and Aging, School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-Sen University, Shenzhen 518100, China. Electronic address: [email protected].
  • 7. Department of General Surgery (Colorectal Surgery), Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China. Electronic address: [email protected].
  • 8. Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou 510055, China; Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing 210029, China. Electronic address: [email protected].
  • 9. State Key Laboratory of Anti-Infective Drug Discovery and Development, National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China. Electronic address: [email protected].
PMID: 42105768 DOI: 10.1016/j.xcrm.2026.102801
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+ 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.

Keywords
colorectal cancer; dendritic cells; engineered bacteria; immunotherapy; interleukin-12; quorum sensing; tumor microenvironment.
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