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In this study, we reasoned that donor autoantibodies from AML recipients cured following allogeneic transplant and responsible for the graft-versus-leukemia effect could be engineered to create effective CAR T cells. We generated CAR T cells against one such antigen\u2014U5 snRNP200, an RNA helicase localized to the AML cell surface and absent from normal hematopoietic precursors. Anti-U5 snRNP200 CAR T cells were effective in human and syngeneic models of AML as well as B-cell acute lymphoblastic leukemia, a setting where surface U5 snRNP200 is also present. Armoring CAR T cells with IL-18 led to antigen gain on AML, durable remission, and protection from AML rechallenge. These data thereby identify a CAR T-cell platform that addresses prior limitations in tumor selectivity and safety for patients with acute leukemias.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>A major hurdle in developing cell therapies for patients with AML has been that there are few antigens that discriminate AML from vital normal hematopoiesis. In this study, we harnessed alloantibodies from patients with AML who were cured following allotransplant targeting a cell surface RNA-binding protein to create an effective cell therapy for acute leukemias.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-25-0920","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T14:25:34Z","timestamp":1777559134000},"page":"2085-2107","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Development of CAR T Cells Targeting a Surface RNA-Binding Protein for the Treatment of Acute Leukemias"],"prefix":"10.1158","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3444-4198","authenticated-orcid":false,"given":"Takeshi","family":"Fujino","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02yrq0923","id-type":"ROR","asserted-by":"publisher"}],"name":"Memorial Sloan Kettering Cancer Center 1 Molecular 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