Chemokines expressed by engineered bacteria recruit and orchestrate antitumor immunity
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- Thomas M. Savage
- Department of Microbiology and Immunology, Columbia University, New York, NY, USA.
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- Rosa L. Vincent
- Department of Biomedical Engineering, Columbia University, New York, NY, USA.
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- Sarah S. Rae
- Department of Microbiology and Immunology, Columbia University, New York, NY, USA.
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- Lei Haley Huang
- Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.
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- Alexander Ahn
- Department of Microbiology and Immunology, Columbia University, New York, NY, USA.
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- Kelly Pu
- Department of Biomedical Engineering, Columbia University, New York, NY, USA.
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- Fangda Li
- Department of Microbiology and Immunology, Columbia University, New York, NY, USA.
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- Kenia de los Santos-Alexis
- Department of Microbiology and Immunology, Columbia University, New York, NY, USA.
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- Courtney Coker
- Department of Biomedical Engineering, Columbia University, New York, NY, USA.
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- Tal Danino
- Department of Biomedical Engineering, Columbia University, New York, NY, USA.
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- Nicholas Arpaia
- Department of Microbiology and Immunology, Columbia University, New York, NY, USA.
書誌事項
- 公開日
- 2023-03-10
- DOI
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- 10.1126/sciadv.adc9436
- 公開者
- American Association for the Advancement of Science (AAAS)
説明
<jats:p> Tumors use multiple mechanisms to actively exclude immune cells involved in antitumor immunity. Strategies to overcome these exclusion signals remain limited due to an inability to target therapeutics specifically to the tumor. Synthetic biology enables engineering of cells and microbes for tumor-localized delivery of therapeutic candidates previously unavailable using conventional systemic administration techniques. Here, we engineer bacteria to intratumorally release chemokines to attract adaptive immune cells into the tumor environment. Bacteria expressing an activating mutant of the human chemokine CXCL16 (hCXCL16 <jats:sup>K42A</jats:sup> ) offer therapeutic benefit in multiple mouse tumor models, an effect mediated via recruitment of CD8 <jats:sup>+</jats:sup> T cells. Furthermore, we target the presentation of tumor-derived antigens by dendritic cells, using a second engineered bacterial strain expressing CCL20. This led to type 1 conventional dendritic cell recruitment and synergized with hCXCL16 <jats:sup>K42A</jats:sup> -induced T cell recruitment to provide additional therapeutic benefit. In summary, we engineer bacteria to recruit and activate innate and adaptive antitumor immune responses, offering a new cancer immunotherapy strategy. </jats:p>
収録刊行物
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- Science Advances
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Science Advances 9 (10), eadc9436-, 2023-03-10
American Association for the Advancement of Science (AAAS)
