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Probiotic-guided CAR-T cells for solid tumor targeting
Open accessAbstract
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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“Moreover, E. coli Nissle 1917 can be programmed to target tumor microenvironments and deliver CAR antigens and enhance CAR-T cell tumor cell killing.177”
From Melanoma and microbiota: Current understanding and future directions (2024) · cites this paper as [177]
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Metadata
- 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
- Venue
- Science
- Published
- 2023-10-13
- Volume
- 382
- Issue
- 6667
- Pages
- 211-218
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- 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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