Evaluation of dasatinib and ponatinib for the control of CD123 CAR-T cell functionalities.

ABSTRACT: CD123 CAR-T cells (CAR123) represent a promising therapeutic approach for blastic plasmacytoid dendritic cell neoplasm (BPDCN) and CD123⁺ acute myeloid leukemia (AML). However, the pro-inflammatory environment resulting from CAR-T cell activation can induce CD123 upregulation on endothelial cells and potential on-target/off-tumor toxicity. We evaluated the capacity of two tyrosine kinase inhibitors (TKIs), dasatinib and ponatinib, to reversibly inhibit CAR-T cell functions. Using different in vitro models of CAR123 co-culture with BPDCN and AML cell lines, we show that both TKIs reduce CAR123 activation phenotype (CD69 and CD25), tumor necrosis factor α (TNF-α) and interferon-γ (IFN-γ) secretion; degranulation (CD107a); and killing of leukemia cells. Moreover, this inhibi

SUBMITTER: Mantion CF 

PROVIDER: S-EPMC12752794 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature