Work

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

Year: 2025

Type: article

Abstract: 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 inhibition was reversible after elimination of the TKIs. However, only dasatinib was effective at clinically relevant concentrations; 50 nM inhibited TNF-α and IFN-γ secretion, with only a slight reduction in cytotoxicity toward leukemia cells and allowed effective control of CAR-T cell cytotoxicity against endothelial cells in relation to the inhibition of cytokine secretion. Thus, dasatinib could be used to minimize potential CAR123 toxicity toward endothelial cells without compromising its anti-leukemic effects. However, a higher dose could be used to completely inhibit CAR-T cell functionality in the event of toxicity.

Source: Molecular Therapy Oncology

DOI: 10.1016/j.omton.2025.201097