ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026
A Drug-Gated, Modular STAb-T Immunotherapy With External Control.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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24 authors.
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Abstract
Living cell therapies lack robust, reversible mechanisms for externally controlling therapeutic activity after administration, limiting their safety and clinical adaptability. Here we engineer a drug-gated cellular immunotherapy platform in which T cells function as programmable factories that secrete two inactive antibody modules whose extracellular assembly into a functional bispecific T cell engager (TCE) is controlled by a small-molecule input. Using a rapalog-inducible FKBP-FRB* heterodimerization switch, we design a split CD19 × CD3 engager architecture that remains inactive in the absence of drug and assembles on demand upon rapalog exposure. A 2A-peptide bicistronic construct enables coordinated expression and secretion of both modules, allowing precise drug-dependent control of TCE formation in situ. Drug administration quantitatively regulates T cell activation and cytotoxicity against CD19
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