| First Author | Maluski M | Year | 2019 |
| Journal | J Clin Invest | Volume | 129 |
| Issue | 12 | Pages | 5108-5122 |
| PubMed ID | 31479431 | Mgi Jnum | J:297079 |
| Mgi Id | MGI:6452272 | Doi | 10.1172/JCI126350 |
| Citation | Maluski M, et al. (2019) Chimeric antigen receptor-induced BCL11B suppression propagates NK-like cell development. J Clin Invest 129(12):5108-5122 |
| abstractText | 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. |
