biostudies-literatureUnknown10(4)Rohrbacher L<h4>Abstract</h4>T-cell-based immunotherapies have revolutionized treatment paradigms in B-cell malignancies, yet their translation to acute myeloid leukemia (AML) has been hindered by a scarcity of tumor-restricted antigens and the risk of on-target off-leukemia toxicity. FLT3 has emerged as a promising therapeutic target with limited expression in healthy hematopoietic tissues. Here, we performed a head-to-head preclinical comparison of an FMS-like tyrosine kinase 3 (FLT3)-directed bispecific T-cell engager (BiTE) molecule and second-generation FLT3-specific chimeric antigen receptor (CAR) T cells. Both approaches induced potent cytotoxicity against AML cell lines and primary patient-derived cells but spared healthy hematopoietic stem and progenitor cells in vitro. Despite similar short-Blood advances1179-1193https://www.ebi.ac.uk/biostudies/studies/S-EPMC12917520biostudies-literatureFLT3-directed BiTE molecules vs CAR T cells in AML: costimulatory signals mitigate T-cell exhaustion.PMC12917520Hoffmann GVGoldstein RLStadler HHanel GTheurich SKobold SSubklewe MBrauchle BRohrbacher LKirmaier MEPhilipp NArvedson TMarcinek AKazerani MGottschlich ARichter DNixdorf DMarkl FStraub TMagno GBucklein VfalseFLT3-directed BiTE molecules vs CAR T cells in AML: costimulatory signals mitigate T-cell exhaustion.<h4>Abstract</h4>T-cell-based immunotherapies have revolutionized treatment paradigms in B-cell malignancies, yet their translation to acute myeloid leukemia (AML) has been hindered by a scarcity of tumor-restricted antigens and the risk of on-target off-leukemia toxicity. FLT3 has emerged as a promising therapeutic target with limited expression in healthy hematopoietic tissues. Here, we performed a head-to-head preclinical comparison of an FMS-like tyrosine kinase 3 (FLT3)-directed bispecific T-cell engager (BiTE) molecule and second-generation FLT3-specific chimeric antigen receptor (CAR) T cells. Both approaches induced potent cytotoxicity against AML cell lines and primary patient-derived cells but spared healthy hematopoietic stem and progenitor cells in vitro. Despite similar short-2026-01-01T00:00:00Z2026 Feb2026-07-16T09:57:53.858Z2026-07-09T10:49:41.373ZS-EPMC129175204132459410.1182/bloodadvances.2025018168