TY - JOUR AU - Maluski, Marcel AU - Ghosh, Arnab AU - Herbst, Jessica AU - Scholl, Vanessa AU - Baumann, Rolf AU - Huehn, Jochen AU - Geffers, Robert AU - Meyer, Johann AU - Maul, Holger AU - Eiz-Vesper, Britta AU - Krueger, Andreas AU - Schambach, Axel AU - van den Brink, Marcel R.M. AU - Sauer, Martin G. T1 - Chimeric antigen receptor–induced BCL11B suppression propagates NK-like cell development PY - 2019/12/02/ AB - 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 during early phases of ex vivo generation of lymphoid progenitors suppressed BCL11B, leading to suppression of T cell–associated gene expression and acquisition of NK cell–like properties. Upon adoptive transfer into hematopoietic stem cell transplant recipients, CAR-expressing lymphoid progenitors differentiated into CAR-induced killer (CARiK) cells that mediated potent antigen-directed antileukemic activity even across MHC barriers. CD28 and active immunoreceptor tyrosine–based activation motifs were critical for a functional CARiK phenotype. These results give important insights into differentiation of murine and human lymphoid progenitors driven by synthetic CAR transgene expression and encourage further evaluation of ex vivo–generated CARiK cells for targeted immunotherapy. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI126350 VL - 129 IS - 12 UR - https://doi.org/10.1172/JCI126350 SP - 5108 EP - 5122 PB - The American Society for Clinical Investigation ER -