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Loss of endocytic activity exacerbates the effects of trogocytosis, the bidirectional transfer of tumor target antigens and CARs between malignant cells and CARTs, resulting in CART dysfunction and fratricide. Constitutive expression of Rab5 within the CARTs reduced fratricide by reducing the amount of trogocytosed antigens on the cell surface, while simultaneously enhancing CAR availability through dissociation of CAR from target, recycling unbound CAR back to the plasma membrane, and limiting CAR capture by tumor cells. Rab5-expressing CARTs exhibited superior antitumor activity in both BCMA-CARTs isolated from the bone marrow of treated patients and mesothelin-specific CARTs in a solid tumor model. These studies uncover an unexpected relationship between endocytosis and CART function and suggest that pairing Rab5 with CAR expression could improve the clinical efficacy of CART therapy.<\/jats:p>","DOI":"10.1084\/jem.20252564","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T06:21:02Z","timestamp":1774592462000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Rab5 improves CAR T cell efficacy via reducing fratricide and maintaining surface CAR levels"],"prefix":"10.1084","volume":"223","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3301-8824","authenticated-orcid":true,"given":"Meidi","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA 1"},{"name":"Center for Cellular Immunotherapies, 2 University of Pennsylvania, Perelman School of Medicine, Philadelphia, 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