Linperlisib Potentiates MUC1-Tn CAR T Cell Therapy by Suppressing the EGR1/DUSP2 Axis to Combat T-Cell Acute Lymphoblastic Leukemia

Highlight

• MUC1-Tn is overexpressed in T-cell acute lymphoblastic leukemia (T-ALL) and serves as an effective target for CAR T cell therapy.
• Linperlisib, a selective PI3Kδ inhibitor, enhances MUC1-Tn CAR T cell cytotoxicity and persistence both in vitro and in xenograft T-ALL models.
• Linperlisib prevents CAR T cell exhaustion through suppression of the EGR1/DUSP2 signaling axis and promotes mitochondrial fusion and respiratory function.
• This combination approach offers a promising strategy to overcome CAR T cell target-mediated fratricide and functional exhaustion in T-ALL treatment.

Study Background