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<p>Bacterial therapeutics hold great promise for cancer treatment by targeting oxygen-poor tumor regions and complementing existing therapies. However, current approaches often struggle with safety concerns and complex engineering. Developing a safe, effective delivery platform relying entirely on natural bacterial biosynthesis remains a challenge. Here we show that attenuated <i>Serratia marcescens</i> serves as a powerful biohybrid platform for cancer therapy by leveraging its natural biosynthesis of prodigiosin, a photosensitive pigment. We engineer <i>S. marcescens</i> to yield high prodigiosin levels, which exhibit strong intrinsic anti-cancer activity and near-infrared photosensitivity. In female mouse models of melanoma and colorectal cancer, this platform triggers robust systemic immune responses, including enhanced T cell recruitment and long-term memory against tumor recurrence. Furthermore, the bacteria induces tumor cell death via mitophagy, while photothermal properties of prodigiosin enables rapid, light-controlled bacterial clearance post-treatment. These findings establish <i>S. marcescens</i> as a versatile, self-regulating biosynthetic platform for precise and safe cancer immunotherapy.</p>

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A live biohybrid bacterial therapy based on engineered Serratia marcescens

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月7日

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  • Lihao Ji,
  • Tianze Zhu,
  • Tianqi Jiang,
  • Li Wang,
  • Zhonghui Qiu,
  • Shiqi Gao,
  • Yuqi Wang,
  • Jing Wang,
  • Jingyi Zhang,
  • Haomiao Huang,
  • Yunlong Mao,
  • Chen Lin,
  • Jing Zhao,
  • Xiuxiu Wang,
  • Wei Wei

摘要

Bacterial therapeutics hold great promise for cancer treatment by targeting oxygen-poor tumor regions and complementing existing therapies. However, current approaches often struggle with safety concerns and complex engineering. Developing a safe, effective delivery platform relying entirely on natural bacterial biosynthesis remains a challenge. Here we show that attenuated Serratia marcescens serves as a powerful biohybrid platform for cancer therapy by leveraging its natural biosynthesis of prodigiosin, a photosensitive pigment. We engineer S. marcescens to yield high prodigiosin levels, which exhibit strong intrinsic anti-cancer activity and near-infrared photosensitivity. In female mouse models of melanoma and colorectal cancer, this platform triggers robust systemic immune responses, including enhanced T cell recruitment and long-term memory against tumor recurrence. Furthermore, the bacteria induces tumor cell death via mitophagy, while photothermal properties of prodigiosin enables rapid, light-controlled bacterial clearance post-treatment. These findings establish S. marcescens as a versatile, self-regulating biosynthetic platform for precise and safe cancer immunotherapy.