Chimeric antigen receptor-induced BCL11B suppression propagates NK-like cell development.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
van den Brink, Marcel Rm
Sauer, Martin G
MetadataShow full item record
AbstractThe 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.
CitationJ Clin Invest. 2019 Dec 2;129(12):5108-5122. doi: 10.1172/JCI126350.
AffiliationHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- Adding chimeric antigen receptor-induced killer cells to the medical oncology shelf.
- Authors: Brandjes BD, Davila ML
- Issue date: 2019 Dec 2
- Genetically engineered CAR NK cells display selective cytotoxicity against FLT3-positive B-ALL and inhibit in vivo leukemia growth.
- Authors: Oelsner S, Waldmann A, Billmeier A, Röder J, Lindner A, Ullrich E, Marschalek R, Dotti G, Jung G, Große-Hovest L, Oberoi P, Bader P, Wels WS
- Issue date: 2019 Oct 1
- Chimeric antigen receptor-engineered cytokine-induced killer cells overcome treatment resistance of pre-B-cell acute lymphoblastic leukemia and enhance survival.
- Authors: Oelsner S, Wagner J, Friede ME, Pfirrmann V, Genßler S, Rettinger E, Buchholz CJ, Pfeifer H, Schubert R, Ottmann OG, Ullrich E, Bader P, Wels WS
- Issue date: 2016 Oct 15
- Continuously expanding CAR NK-92 cells display selective cytotoxicity against B-cell leukemia and lymphoma.
- Authors: Oelsner S, Friede ME, Zhang C, Wagner J, Badura S, Bader P, Ullrich E, Ottmann OG, Klingemann H, Tonn T, Wels WS
- Issue date: 2017 Feb
- CS1-specific chimeric antigen receptor (CAR)-engineered natural killer cells enhance in vitro and in vivo antitumor activity against human multiple myeloma.
- Authors: Chu J, Deng Y, Benson DM, He S, Hughes T, Zhang J, Peng Y, Mao H, Yi L, Ghoshal K, He X, Devine SM, Zhang X, Caligiuri MA, Hofmeister CC, Yu J
- Issue date: 2014 Apr