{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T16:30:39Z","timestamp":1792254639152,"version":"4.4.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Systemic amyloidosis is a protein folding disorder characterized by the extracellular deposition of protein fibrils in tissues and vital organs, leading to dysfunction and mortality. While there are monoclonal antibody-based therapies that promote cell-mediated amyloid clearance in various stages of clinical development, there are currently no treatment options which focus on reducing the tissue amyloid burden. Therefore, the urgent need for a transformative approach to facilitate amyloid clearance and restore organ function remains paramount. We demonstrate that a short, polybasic peptide (p5) can serve as a versatile recognition motif for chimeric antigen receptors in macrophages, enabling pan-amyloid binding and uptake. By comparing CH2- and CH3-spacer designs, quantifying glycan interactions, and establishing opsonization- and complement-dependent enhancement, we provide a blueprint for peptide-targeted CAR-M engineering beyond conventional scFv recognition. These findings broaden the repertoire of CAR targeting strategies and motivate translational studies of CAR-M for systemic amyloidosis, where established fibrils persist despite precursor-lowering therapies.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1783851","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T05:29:43Z","timestamp":1772774983000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Development and characterization of chimeric antigen receptor macrophages for amyloid clearance"],"prefix":"10.3389","volume":"17","author":[{"given":"Manasi","family":"Balachandran","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Tennessee Health Science Center, College of Medicine","place":["Knoxville, TN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James 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