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We initiated a phase 1 trial (NCT06017258), successfully manufactured and administered CD371\/SAVVY\/IL-18 CAR T cells in 5 patients with relapsed\/refractory AML and observed expansion following a single infusion of 3 \u00d7 104 or 3 \u00d7 105 CAR T cells per kg; 3 patients refractory to \u22655 lines of therapy and postallogeneic transplant exhibited AML clearance and no evidence of graft-versus-host disease. Dose-limiting toxicity in the 2 patients treated with 3 \u00d7 105 CAR T cells per kg dose (prolonged cytopenias with marrow hypoplasia; severe cytokine release syndrome) led to dose reduction to 3 \u00d7 104 CAR T cells per kg in the following 3 patients. Single-cell analyses revealed that circulating CAR T cells in responders included predominantly cytotoxic CD8+ effector T cells 2 weeks after infusion while coexisting natural killer (NK) cells expressed markers of activation. This pilot study highlights the activity of low-dose IL-18 \u201carmored\u201d CAR T cells against refractory AML and their potential to promote CAR T-cell cytotoxicity and innate endogenous antitumor immunity. This trial was registered at www.ClinicalTrials.gov as #NCT06017258.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025029532","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T19:22:10Z","timestamp":1756322530000},"page":"3163-3174","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":49,"title":["CD371-targeted CAR T cells secreting interleukin-18 exhibit robust expansion and clear refractory acute myeloid leukemia"],"prefix":"10.1182","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5248-9117","authenticated-orcid":false,"given":"Mark B.","family":"Geyer","sequence":"first","affiliation":[{"name":"1Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"2Department of Medicine, Cell Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2754-3537","authenticated-orcid":false,"given":"Susan","family":"DeWolf","sequence":"additional","affiliation":[{"name":"1Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Mi","sequence":"additional","affiliation":[{"name":"2Department of Medicine, Cell Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenyon","family":"Weis","sequence":"additional","affiliation":[{"name":"3Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian C.","family":"Shaffer","sequence":"additional","affiliation":[{"name":"2Department of Medicine, Cell Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"4Department of Medicine, Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Briana","family":"Cadzin","sequence":"additional","affiliation":[{"name":"5Department of Nursing, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7807-6775","authenticated-orcid":false,"given":"Devin","family":"McAvoy","sequence":"additional","affiliation":[{"name":"6Immune Discovery and Modeling Service, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe","family":"Katsamakis","sequence":"additional","affiliation":[{"name":"4Department of Medicine, Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Lorenc","sequence":"additional","affiliation":[{"name":"7Pharmacology Program, Graduate School of Medical Sciences, Weill Cornell Medical College, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8003-9535","authenticated-orcid":false,"given":"Alexander M.","family":"Lewis","sequence":"additional","affiliation":[{"name":"3Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna","family":"Gipson","sequence":"additional","affiliation":[{"name":"3Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9660-239X","authenticated-orcid":false,"given":"M. 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