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FLT3L CAR-T cells are an experimental **ligand-based chimeric antigen receptor T cell (CAR-T) therapy** in which T cells are engineered to express a receptor containing the natural FMS-like tyrosine kinase 3 ligand (FLT3L) as the antigen-binding domain instead of the more common scFv (single chain variable fragment). This design specifically targets **FLT3-positive cells**, including those found in acute myeloid leukemia (AML). Unlike traditional FLT3 CAR-T cells, which use antibody fragments to recognize FLT3, FLT3L CAR-T cells utilize the full ligand, potentially offering unique target specificity and signaling. Preclinical studies have shown that FLT3L CAR-T cells can recognize and kill **FLT3-mutated AML** cells (both FLT3-ITD and FLT3 wild-type), with cytotoxicity more pronounced in FLT3-ITD-mutant leukemia. The recognition and cytotoxicity of these cells are not strictly dependent on FLT3 surface density but are sensitive to the FLT3 mutational genotype, offering a novel strategy in distinguishing leukemic from normal cells. There are also advanced CAR-T constructs that co-express FLT3L and cytokines like IL7 to boost intratumoral dendritic cell (DC) and CAR T cell numbers, showing improved survival in models of glioblastoma, suggesting broader possible application in solid tumors[1][4][5][6][7].
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