Cited by 273Bacterial Cancer TherapyCAR-T cell therapy researchImmunotherapy and Immune Responses

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Probiotic-guided CAR-T cells for solid tumor targeting

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Vincent, Rosa L., Gurbatri, Candice R., Li, Fangda, Vardoshvili, Ana, Coker, Courtney, Im, Jongwon, Ballister, Edward R., Rouanne, Mathieu, Savage, Thomas, de los Santos-Alexis, Kenia, Redenti, Andrew, Brockmann, Leonie, Komaranchath, Meghna, Arpaia, Nicholas, Danino, Tal·2023·Science

DOI 10.1126/science.add7034PMC PMC10915968

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Abstract

A major challenge facing tumor-antigen targeting therapies such as chimeric antigen receptor (CAR)–T cells is the identification of suitable targets that are specifically and uniformly expressed on heterogeneous solid tumors. By contrast, certain species of bacteria selectively colonize immune-privileged tumor cores and can be engineered as antigen-independent platforms for therapeutic delivery. To bridge these approaches, we developed a platform of probiotic-guided CAR-T cells (ProCARs), in which tumor-colonizing probiotics release synthetic targets that label tumor tissue for CAR-mediated lysis in situ. This system demonstrated CAR-T cell activation and antigen-agnostic cell lysis that was safe and effective in multiple xenograft and syngeneic models of human and mouse cancers. We further engineered multifunctional probiotics that co-release chemokines to enhance CAR-T cell recruitment and therapeutic response.

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Authors: Vincent, R. L., Gurbatri, C. R., Li, F., Vardoshvili, A., Coker, C., Im, J., Ballister, E. R., Rouanne, M., Savage, T., de los Santos-Alexis, K., Redenti, A., Brockmann, L., Komaranchath, M., Arpaia, N., & Danino, T.
Affiliations: Columbia University (US)
Herbert Irving Comprehensive Cancer Center (US)
Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
Corresponding author: Vincent, Rosa L.
Gurbatri, Candice R.
Danino, Tal
ORCID: Vincent, Rosa L.
Gurbatri, Candice R.
Li, Fangda
Coker, Courtney
Im, Jongwon
Ballister, Edward R.
Rouanne, Mathieu
Savage, Thomas
de los Santos-Alexis, Kenia
Redenti, Andrew
Brockmann, Leonie
Komaranchath, Meghna
Arpaia, Nicholas
Danino, Tal
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2023-10-13
Volume: 382
Issue: 6667
Pages: 211-218
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.add7034
PMC: PMC10915968
OpenAlex: W4387568373
Cited by: 273
References: 65
Citations by year: 2026: 88 · 2025: 114 · 2024: 65 · 2023: 6
FWCI: 35.37
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Science (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Science Foundation (P30CA013696, 1644869)
University of Washington
National Institutes of Health (UL1TR001873, 1644869)
National Cancer Institute (P30CA013696)
National Institute of Biomedical Imaging and Bioengineering (R01EB030352)
National Center for Advancing Translational Sciences
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Bacterial Cancer Therapy
Health Sciences › Medicine › Oncology › CAR-T cell therapy research
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords: chimeric antigen receptor T cells, solid tumors, tumor heterogeneity, cancer immunotherapy
MeSH terms: Receptors, Chimeric Antigen, Animals, Antigens, Neoplasm, Breast Neoplasms, Escherichia coli, Humans, Lymphocyte Activation, T-Lymphocytes, Colorectal Neoplasms, Immunotherapy, Adoptive, Probiotics, Xenograft Model Antitumor Assays, Mice, Cell Engineering

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Probiotic-guided CAR-T cells for solid tumor targeting

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