2. Academic Validation
  3. Orthogonally Engineered Bacteria Capture Metabolically Labeled Tumor Antigens to Improve the Systemic Immune Response in Irradiated Tumors

Orthogonally Engineered Bacteria Capture Metabolically Labeled Tumor Antigens to Improve the Systemic Immune Response in Irradiated Tumors

  • ACS Nano. 2025 Feb 11;19(5):5376-5391. doi: 10.1021/acsnano.4c13320.
Wen Xia 1 2 3 4 5 6,  Zhuo Feng 1,  Yuchen Wang 1,  Ruiqi Lei 1,  Yao Zhou 4,  Yujia Zhuo 1,  Ran Xie 4,  Hong Dong 1,  Xiaozhi Zhao 2,  Xiaoxiang Guan 7,  Jinhui Wu 1 2 3 4 5 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing 210093, China.
  • 2 Department of Andrology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 321 Zhongshan Road, Gulou District, Nanjing 210008, China.
  • 3 Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, China.
  • 4 Chemistry and Biomedicine Innovation Center, Nanjing University, Nanjing 210023, China.
  • 5 Institute of Drug Research and Development & Jiangsu Engineering Center of Biointelligent Materials, Nanjing University, Nanjing 210093, China.
  • 6 Wuxi Xishan NJU Institute of Applied Biotechnology, Anzhen Street, Xishan District, Wuxi 214101, China.
  • 7 Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
PMID: 39889238 DOI: 10.1021/acsnano.4c13320
Abstract

In situ vaccination is considered a promising Cancer Immunotherapy strategy to elicit a tumor-specific T cell response. Live bacteria effectively enhanced the immune response in irradiated tumors as it can activate multiple immune cells. However, the adaptive immune response remains low since bacteria lack the efficient delivery of antigen to dendritic cells (DCs). Here, we show that tumor antigens can be metabolically labeled with azido groups in situ, allowing for their specific capture by orthogonally engineered Salmonella via bioorthogonal chemistry. Subsequently, these antigens are efficiently delivered to DCs through the active movement of the bacteria. Intratumorally injected engineered bacteria captured the labeled antigens and improved their presentation by DCs. This increased the proportion of antigen-specific CD8+ T cells in tumors, further resulting in systemic antitumor effects in the bilateral melanoma mouse model. The antitumor effects were abrogated in Batf3-/- mice or after CD8+ T cell depletion, indicating that systemic antitumor effects were dependent on adaptive immune responses. Overall, our work presents a strategy combining Bacterial engineering and antigen labeling, which may guide the development of in situ vaccines in the future.

Keywords

antigen delivery; biomaterials; engineered bacteria; immunotherapy; in situ vaccination.

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