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Background <p>Bacterial cancer therapies have regained attention as a strategy to remodel the immunosuppressive tumor microenvironment (TME). Engineered bacteria equipped with tumor-targeting moieties can enhance intratumoral specificity; however, safety concerns and the need for repeat dosing limit their translational potential.</p> Methods <p>Here, we developed an aptamer-conjugated engineered bacterial strain (ApCB) carrying CXCL9, and evaluated its tumor-targeting colonization and immunomodulatory effects in a subcutaneous LLC tumor model. After determining the in vitro minimum inhibitory concentration (MIC) of kanamycin and extrapolating an equivalent in vivo dose based on mouse blood volume, we implemented a tail-vein antibiotic administration strategy to precisely regulate intratumoral bacterial burden.</p> Results <p>Antibiotic treatment substantially lowered peak bacterial abundance in tumors while retaining a viable intratumoral bacterial reservoir, allowing sustained bacterial proliferation and periodic CXCL9 release without repeated re-administration of engineered bacteria. In vivo, ApCB–CXCL9 treatment significantly inhibited tumor growth, induced extensive tumor necrosis, decreased Ki67 expression, and increased intratumoral CD8⁺ T-cell infiltration together with elevated effector cytokines (IFN-γ, TNF-α).</p> Conclusion <p>These findings indicate that aptamer-guided engineered bacteria combined with antibiotic-mediated population control can safely and controllably remodel the tumor immune microenvironment, offering a practicable approach for sustained delivery and clinical translation of bacterial immunotherapies.</p>

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Tumor-targeted aptamer-conjugated engineered bacteria for CXCL9 cytokine delivery in non-small cell lung cancer immunotherapy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月27日

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  • Qinghao Gu,
  • Runbang Wang,
  • Lixia Zhang,
  • Di Pan,
  • Chaorong Bian,
  • Erteng Jia,
  • Junda Chang,
  • Hao Zhang

摘要

Background

Bacterial cancer therapies have regained attention as a strategy to remodel the immunosuppressive tumor microenvironment (TME). Engineered bacteria equipped with tumor-targeting moieties can enhance intratumoral specificity; however, safety concerns and the need for repeat dosing limit their translational potential.

Methods

Here, we developed an aptamer-conjugated engineered bacterial strain (ApCB) carrying CXCL9, and evaluated its tumor-targeting colonization and immunomodulatory effects in a subcutaneous LLC tumor model. After determining the in vitro minimum inhibitory concentration (MIC) of kanamycin and extrapolating an equivalent in vivo dose based on mouse blood volume, we implemented a tail-vein antibiotic administration strategy to precisely regulate intratumoral bacterial burden.

Results

Antibiotic treatment substantially lowered peak bacterial abundance in tumors while retaining a viable intratumoral bacterial reservoir, allowing sustained bacterial proliferation and periodic CXCL9 release without repeated re-administration of engineered bacteria. In vivo, ApCB–CXCL9 treatment significantly inhibited tumor growth, induced extensive tumor necrosis, decreased Ki67 expression, and increased intratumoral CD8⁺ T-cell infiltration together with elevated effector cytokines (IFN-γ, TNF-α).

Conclusion

These findings indicate that aptamer-guided engineered bacteria combined with antibiotic-mediated population control can safely and controllably remodel the tumor immune microenvironment, offering a practicable approach for sustained delivery and clinical translation of bacterial immunotherapies.