Probiotic-guided CAR-T cells for solid tumor targeting

• 成果类型: Article
• 署名作者: 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
• 署名单位: Columbia University; Columbia University; Columbia University; Columbia University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10650
• DOI: 10.1126/science.add7034
• 发表日期: 2023-10-13
• 页码: 211-218
• 关键词: chimeric antigen receptors; phase-i; affinity; tlr5

摘要

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.