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Thermal-responsive activation of engineered bacteria to trigger antitumor immunity post microwave ablation therapy

Author

Listed:
  • Yumin Wu

    (Soochow University)

  • Bo Liu

    (Soochow University)

  • Yifan Yan

    (Soochow University)

  • Chuntao Gong

    (InnoBM Pharmaceuticals)

  • Kaiwei Wang

    (Soochow University)

  • Nanhui Liu

    (Soochow University)

  • Yujie Zhu

    (Soochow University)

  • Maoyi Li

    (Soochow University)

  • Chunjie Wang

    (Soochow University)

  • Yizhe Yang

    (Soochow University)

  • Liangzhu Feng

    (Soochow University)

  • Zhuang Liu

    (Soochow University)

Abstract

Incomplete tumor removal after microwave ablation (MWA), a widely used hyperthermia-based therapy, can result in tumor recurrence. Herein, attenuated Salmonella typhimurium VNP20009 is engineered to release interleukin-15&interleukin-15-receptor-alpha (IL-15&IL-15Rα) in response to mildly elevated temperature. Such 15&15R@VNP colonizes in tumors upon intravenous injection, and the expression of IL-15&IL-15Rα is triggered by MWA. Anti-tumor immune responses are elicited, efficiently suppressing tumor growth even after incomplete microwave ablation. We further design VNP20009 with thermal-responsive co-expression of both IL-15&IL-15Rα and soluble programmed cell death protein (sPD-1). Such sPD-1-15&15R@VNP can also reverse the functional suppression of immune cells driven by PD-1/PD-L1 axis, reinvigorating progenitor exhausted T cells, a critical subset of cytotoxic T lymphocytes responsive to immune checkpoint blockade. Such thermal-responsive engineered bacteria are thus a promising adjuvant therapy to potentiate tumor ablation therapies via effectively activating antitumor immunity.

Suggested Citation

  • Yumin Wu & Bo Liu & Yifan Yan & Chuntao Gong & Kaiwei Wang & Nanhui Liu & Yujie Zhu & Maoyi Li & Chunjie Wang & Yizhe Yang & Liangzhu Feng & Zhuang Liu, 2024. "Thermal-responsive activation of engineered bacteria to trigger antitumor immunity post microwave ablation therapy," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54883-x
    DOI: 10.1038/s41467-024-54883-x
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