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Genetic engineering of macrophages using chimeric antigen receptor (CAR) technology \u2212 enabling recognition and phagocytosis of neoplastic cells \u2212 is emerging as a potential therapeutic strategy against solid tumors. Human induced pluripotent stem cells (iPSCs) provide a renewable platform for the efficient differentiation of functionally competent macrophages. In this study, we engineered human iPSC\u2010derived CAR macrophages (iCAR\u2010M) targeting interleukin\u201013 receptor subunit alpha 2 (IL\u201013R\u03b12). Pan\u2010tumor transcriptomic and immunohistochemical analyses revealed that IL\u201013R\u03b12, a tumor\u2010associated antigen, was overexpressed in human glioblastoma (GBM), uterine carcinosarcoma (UCS), and melanoma specimens.\n In vitro<\/jats:italic>\n phagocytosis assays revealed target\u2010specific clearance of IL\u201013R\u03b12\u2010positive tumor cells by iCAR\u2010M. Intracranial administration of iCAR\u2010M potently suppressed tumor growth, enhanced intratumoral cytotoxic T\u2010cell infiltration, and prolonged the survival of humanized, immunocompetent mice bearing GBM xenografts. The administered iCAR\u2010M maintained phagocytic capacity\n in vivo<\/jats:italic>\n and acquired an M1\u2010like pro\u2010inflammatory phenotype. Comprehensive safety assessment revealed no detectable evidence of systemic toxicity or treatment\u2010related neurotoxicity. Collectively, these results demonstrate the potent efficacy and favorable safety profile of iPSC\u2010derived, IL\u201013R\u03b12\u2010targeted CAR macrophages, supporting their therapeutic potential against solid tumors. \u00a9 2026 The Pathological Society of Great Britain and Ireland.\n <\/jats:p>","DOI":"10.1002\/path.70063","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T11:16:39Z","timestamp":1776251799000},"page":"322-336","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Human induced pluripotent stem cell\u2010derived chimeric antigen receptor\u2010macrophages eradicate\n IL<\/scp>\n \u2010\n 13R\u03b12<\/scp>\n \u2010positive solid tumors"],"prefix":"10.1002","volume":"269","author":[{"given":"Ying","family":"Yang","sequence":"first","affiliation":[{"name":"Institute of Pathology & Southwest Cancer Center, the First Affiliated Hospital (Southwest Hospital) and School 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