biostudies-literatureVincent RLNIBIB NIH HHSNCATS NIH HHSNCI NIH HHS211-218https://www.ebi.ac.uk/biostudies/studies/S-EPMC10915968biostudies-literatureUnknown382(6667)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.Science (New York, N.Y.)Probiotic-guided CAR-T cells for solid tumor targeting.PMC10915968R01 EB030352UL1 TR001873P30 CA013696Li FRouanne MSavage TIm JKomaranchath MCoker CArpaia NDanino Tde Los Santos-Alexis KVincent RLVardoshvili AGurbatri CRBrockmann LBallister ERRedenti AfalseProbiotic-guided CAR-T cells for solid tumor targeting.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.2023-01-01T00:00:00Z2023 Oct2025-04-26T20:15:12.233Z2025-04-06T16:26:05.626ZS-EPMC109159683782464010.1126/science.add7034