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Though chimeric antigen receptor (CAR) T cell therapies have shown notable effectiveness in hematologic malignancies, their efficiency against solid tumors is limited by tumor heterogeneity, immunosuppressive tumor microenvironments (TMEs), and off-target toxicities. By replacing the conventional scFv domain with the extracellular domains of Fc\u03b3Rs\u2014including CD16a, CD32a, or CD64a\u2014Fc\u03b3R-CR T cells provide a unique method allowing T cells to be steered by monoclonal antibodies (mAbs) targeting several tumor-associated antigens (TAAs). Emphasizing their advantages in flexibility, reversibility, and compatibility with present antibody therapy, the review clarifies the mechanisms of action, preclinical developments, and clinical promise of Fc\u03b3R-CR T cells. Future directions include increasing specificity by means of affinity-engineered Fc\u03b3Rs and Fc-modified monoclonal antibodies, generating universal allogeneic Fc\u03b3R-CR T cells for immediate use, using regulatable expression systems to improve safety, and combining these engineered cells with immune checkpoint inhibitors or metabolic modulators to overcome tumor microenvironment resistance. Overall, Fc\u03b3R-CR T cells offer a hopeful next-generation immunotherapeutic approach able to handle the current CAR T cell constraints and change precision oncology, particularly for aggressive and treatment-resistant solid cancers.<\/jats:p>","DOI":"10.1186\/s12935-026-04258-7","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T12:05:46Z","timestamp":1776341146000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fc\u03b3R-driven chimeric receptor T cells in cancer therapy: a novel frontier in antibody-guided immunotherapy"],"prefix":"10.1186","volume":"26","author":[{"given":"Hany E.","family":"Marei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Pozzoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Caratelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Cenciarelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"issue":"3","key":"4258_CR1","first-page":"209","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. 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