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While switch\u2010controlled CAR\u2010T holds great promise, challenges remain in achieving accurate activation, reducing immunogenicity, and preventing off\u2010target effects. Here we present a novel inducible ON\u2010switch CAR design that leverages plant hormone signaling components to achieve controllable T cell activation. By engineering a receptor system integrating the plant auxin receptor AFB1 with its co\u2010receptor IAA7, we enable ligand\u2010dependent interactions triggered by the plant hormone auxins. This design allows rapid, reversible, and dose\u2010dependent T cell activation, resulting in potent cytotoxicity against B\u2010cell lymphoma in vitro and in vivo. Notably, auxCAR\u2010T cells controlled by synthetic auxin analogs maintain a favorable memory phenotype and exhibit reduced functional exhaustion during treatment, leading to improved therapeutic efficacy. Our plant hormone\u2010based orthogonal system overcomes key limitations of existing switch systems and advances the development of precision CAR\u2010T therapies.<\/jats:p>","DOI":"10.1002\/advs.77020","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T15:31:20Z","timestamp":1786462280000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Repurposing a Small Molecule Plant Hormone as a Tunable ON\u2010Switch for CAR\u2010T Cell Immunotherapy"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3709-364X","authenticated-orcid":false,"given":"Hongxiang","family":"Zeng","sequence":"first","affiliation":[{"name":"Faculty of Synthetic Biology and Institute of Cell and Gene Technology Shenzhen University of Advanced Technology  Shenzhen China"},{"name":"State Key Laboratory of Quantitative Synthetic Biology Shenzhen Institute of Synthetic Biology Shenzhen Institutes 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