Chimeric Antigen Receptor-Induced Bcl11b Suppression Propagates Natural Killer-Like Cell Development

The transcription factor B Cell CLL/Lymphoma 11B (BCL11B) is indispensable for T lineage development of lymphoid progenitors. Here we show that chimeric antigen receptor (CAR) expression early in ex vivo generated lymphoid progenitors suppresses Bcl11b, leading to suppression of T cell-associated gene expression and acquisition of natural killer (NK) cell-like properties. These results give important insights into differentiation of murine and human lymphoid progenitors driven by synthetic CAR transgene-expression and inform the potential use of ex vivo generated CARiK cells as a broadly applicable product for targeted immunotherapy.

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Maluski M, Ghosh A, Herbst J, Scholl V, Baumann R, Huehn J, Geffers R, Meyer J, Maul H, Eiz-Vesper B, Krueger A, Schambach A, van den Brink MR, Sauer MG