Adapter CAR T cells to counteract T-cell exhaustion and enable flexible targeting in AML

This study established a Fab-based adapter CAR (AdCAR) T-cell platform with flexible targeting and control of AdCAR T-cell activation. Utilizing AML cell lines and a long-term culture assay for primary AML cells, we demonstrated AML-specific cytotoxicity using anti-CD33, anti-CD123, and anti-CLL1 adapter molecules in vitro and in vivo. Notably, we show the feasibility of the sequential application of adapter molecules of different specificity in primary AML co-cultures for the first time. Furthermore, using the AML platform, the authors demonstrated that introducing treatment-free intervals could counteract chronic T-cell stimulation and exhaustion.