Current AML treatments have limitations, with relapse being common. This study presents a novel Fab-based adapter CAR (4dCAR T-cell) platform for AML immunotherapy, addressing challenges in target antigen heterogeneity, safety, and T-cell dysfunction. In vitro and in vivo experiments demonstrated AML-specific cytotoxicity using anti-CD33, anti-CD123, and anti-CLL1 adapter molecules. Sequential application of adapter molecules with different specificities proved feasible. The platform also mitigates T-cell exhaustion through treatment-free intervals.

D. Nixdorf, M. Sponheimer, D. Berghammer, F. Engert, U. Bader, N. Philipp, M. Kazerani, T. Straub, L. Rohrbacher, L. Wange, S. Dapa, D. Atar, C. M. Seitz, K. Brandstetter, A. Linder, M. von Bergvelt, H. Leonhardt, J. Mittelstädt, A. Kaiser, V. Bücklein, M. Sukbwele