First published September 3, 2019 - More info
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 suppressed BCL11B, leading to suppression of T cell-associated gene expression and acquisition of natural killer (NK) cell-like properties. Upon adoptive transfer into hematopoietic stem cell transplant recipients they differentiated into CAR-induced killer cells (CARiK) that mediated potent antigen-directed antileukemic activity even across MHC barriers. A CD28 and active immune-receptor-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.