Development of MUC1-Tn CAR T Cells for T-ALL
Wei J-Y, Liu Z-W, Lu Q-S, et al. Linperlisib Enhances MUC1-Tn CAR T Cell Efficacy by Inhibiting EGR1/DUSP2 Axis to Prevent CAR T Cell Exhaustion. Leukemia. 2026; (doi: 10.1038/s41375-026-03021-1).
Chimeric antigen receptor (CAR) T-cell therapy has limited efficacy against T-cell acute lymphoblastic leukemia (T-ALL), but researchers have identified a target antigen and approach that they believe could be a game-changer. The antigen of interest is Mucin1-Thomsen-nouvelle (MUC1-Tn), and it is highly expressed in T-ALL. Scientists engineered MUC1-Tn CAR T cells and subsequently validated them as both safe and efficacious in cell line-derived xenograft and patient-derived xenograft models. To enhance the cells' durability, the team added linperlisib during CAR T-cell expansion, which delayed T-cell and CAR T-cell exhaustion and curtailing exhaustion marker expression. The result was a significant improvement in the potency and functional persistence of the MUC1-Tn CAR-T cells, likely through linperlisib's suppression of early growth response protein 1 (EGR1) and dual specificity phosphatase 2 (DUSP2).