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Published on: June 14, 2024
Probiotic-guided CAR-T cells for solid tumor targeting
Rosa L Vincent1, Candice R Gurbatri1, Fangda Li2
1Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.
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.
Insights
Engineered bacteria deliver synthetic targets to tumors, guiding chimeric antigen receptor (CAR)-T cells for antigen-agnostic cancer cell killing. This probiotic-guided CAR-T cell (ProCAR) therapy shows promise in preclinical cancer models.
Area of Science:
- Oncology
- Microbiology
- Immunotherapy
Background:
- Solid tumor targeting therapies face challenges due to tumor heterogeneity and lack of specific antigens.
- Bacteria can selectively colonize tumors and serve as engineered therapeutic delivery platforms.
Purpose of the Study:
- To develop a novel platform combining probiotics and CAR-T cells for targeted cancer therapy.
- To overcome limitations of antigen-specific targeting in solid tumors.
Main Methods:
- Engineered probiotics to release synthetic tumor targets.
- Developed probiotic-guided CAR-T cells (ProCARs) for in situ tumor labeling and lysis.
- Tested ProCARs in xenograft and syngeneic models of human and mouse cancers.
- Engineered probiotics to co-release chemokines for enhanced CAR-T cell recruitment.
Main Results:
- ProCARs demonstrated CAR-T cell activation and antigen-agnostic tumor cell lysis.
- The system was safe and effective in multiple preclinical cancer models.
- Multifunctional probiotics enhanced CAR-T cell recruitment and therapeutic response.
Conclusions:
- Probiotic-guided CAR-T cells offer a viable strategy for targeting solid tumors.
- This approach enables antigen-independent cancer cell killing and enhances immunotherapy.
- Further development of engineered probiotics can improve CAR-T cell-based cancer therapies.
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