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To address these challenges and enhance CAR T cell functionality, we leveraged meditope technology, a lock-and-key platform where Fab regions of antibodies are modified to bind a small cyclic peptide termed meditope (meP). We developed a panel of meditope-enabled Fab-based CARs (meCARs), which show selective binding to the meP and comparable activity to traditional single-chain variable fragment (scFv)-based CARs. Focusing on HER2-targeted meCARs for evaluating platform utility, we exploited the modularity of the meditope platform to detect meCAR T cells using meP-fused fluorescent agents, promote meCAR T cell expansion via meP-fused IL-15 cytokine, and broaden tumor antigen targeting through meP-fused antibodies to address tumor heterogeneity. These findings establish the meditope technology as a versatile strategy to augment CAR T cell functionality and overcome key limitations of current CAR-based therapies.<\/jats:p>","DOI":"10.64898\/2026.04.02.715976","type":"posted-content","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T02:45:13Z","timestamp":1775529913000},"source":"Crossref","is-referenced-by-count":0,"title":["Meditope-Enabled Chimeric Antigen Receptors Facilitate Plug-and-Play Control of T Cells"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8933-0799","authenticated-orcid":false,"given":"Cheng-Fu","family":"Kuo","sequence":"first","affiliation":[{"name":"Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA"},{"name":"Irell and Manella Graduate School of Biological Sciences, City of Hope, Duarte, 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