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Immunotherapy with engineered bacteria by targeting the STING pathway for anti-tumor immunity

Author

Listed:
  • Daniel S. Leventhal

    (Synlogic, Inc.)

  • Anna Sokolovska

    (Synlogic, Inc.)

  • Ning Li

    (Synlogic, Inc.)

  • Christopher Plescia

    (Synlogic, Inc.)

  • Starsha A. Kolodziej

    (Synlogic, Inc.)

  • Carey W. Gallant

    (Synlogic, Inc.)

  • Rudy Christmas

    (Synlogic, Inc.)

  • Jian-Rong Gao

    (Synlogic, Inc.)

  • Michael J. James

    (Synlogic, Inc.)

  • Andres Abin-Fuentes

    (Synlogic, Inc.)

  • Munira Momin

    (Synlogic, Inc.)

  • Christopher Bergeron

    (Synlogic, Inc.)

  • Adam Fisher

    (Synlogic, Inc.)

  • Paul F. Miller

    (Synlogic, Inc.)

  • Kip A. West

    (Synlogic, Inc.)

  • Jose M. Lora

    (Synlogic, Inc.)

Abstract

Synthetic biology is a powerful tool to create therapeutics which can be rationally designed to enable unique and combinatorial functionalities. Here we utilize non-pathogenic E coli Nissle as a versatile platform for the development of a living biotherapeutic for the treatment of cancer. The engineered bacterial strain, referred to as SYNB1891, targets STING-activation to phagocytic antigen-presenting cells (APCs) in the tumor and activates complementary innate immune pathways. SYNB1891 treatment results in efficacious antitumor immunity with the formation of immunological memory in murine tumor models and robust activation of human APCs. SYNB1891 is designed to meet manufacturability and regulatory requirements with built in biocontainment features which do not compromise its efficacy. This work provides a roadmap for the development of future therapeutics and demonstrates the transformative potential of synthetic biology for the treatment of human disease when drug development criteria are incorporated into the design process for a living medicine.

Suggested Citation

  • Daniel S. Leventhal & Anna Sokolovska & Ning Li & Christopher Plescia & Starsha A. Kolodziej & Carey W. Gallant & Rudy Christmas & Jian-Rong Gao & Michael J. James & Andres Abin-Fuentes & Munira Momin, 2020. "Immunotherapy with engineered bacteria by targeting the STING pathway for anti-tumor immunity," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16602-0
    DOI: 10.1038/s41467-020-16602-0
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    Cited by:

    1. Jun Zhou & Maoyi Li & Qiufang Chen & Xinjie Li & Linfu Chen & Ziliang Dong & Wenjun Zhu & Yang Yang & Zhuang Liu & Qian Chen, 2022. "Programmable probiotics modulate inflammation and gut microbiota for inflammatory bowel disease treatment after effective oral delivery," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Mohamad H. Abedi & Michael S. Yao & David R. Mittelstein & Avinoam Bar-Zion & Margaret B. Swift & Audrey Lee-Gosselin & Pierina Barturen-Larrea & Marjorie T. Buss & Mikhail G. Shapiro, 2022. "Ultrasound-controllable engineered bacteria for cancer immunotherapy," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    3. Jung Hun Park & Gábor Holló & Yolanda Schaerli, 2024. "From resonance to chaos by modulating spatiotemporal patterns through a synthetic optogenetic oscillator," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    4. Ling Huang & Wei Tang & Lina He & Mengke Li & Xian Lin & Ao Hu & Xindi Huang & Zhouyu Wu & Zhiyong Wu & Shiyun Chen & Yangbo Hu, 2024. "Engineered probiotic Escherichia coli elicits immediate and long-term protection against influenza A virus in mice," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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