Citations to this article
Citation Information: J Clin Invest. 2019;129(12):5108-5122. https://doi.org/10.1172/JCI126350.
Abstract
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.
Authors
Marcel Maluski, Arnab Ghosh, Jessica Herbst, Vanessa Scholl, Rolf Baumann, Jochen Huehn, Robert Geffers, Johann Meyer, Holger Maul, Britta Eiz-Vesper, Andreas Krueger, Axel Schambach, Marcel R.M. van den Brink, Martin G. Sauer
Citations to this article (15)
| Title and authors | Publication | Year |
|---|---|---|
|
Targeting BCL11B in CAR-engineered lymphoid progenitors drives NK-like cell development with prolonged anti-leukemic activity
Baatz F, Ghosh A, Herbst J, Polten S, Meyer J, Rhiel M, Maetzig T, Geffers R, Rothe M, Bastone AL, John-Neek P, Frühauf J, Eiz-Vesper B, Bonifacius A, Falk CS, Kaisenberg CV, Cathomen T, Schambach A, van den Brink MR, Hust M, Sauer MG |
Molecular Therapy | 2025 |
|
Strength of CAR signaling determines T versus ILC2 lineage differentiation from pluripotent stem cells
Suwen Li, Chloe Wang, Amélie Montel-Hagen, Ho-Chung Chen, Shawn Lopez, Olivia Zhou, William Satyadi, Carlos Botero, Steven Tsai, Claudia Wong, David Casero, Gay Crooks, Christopher Seet |
Cell Reports | 2023 |
|
BCL11B and the NuRD complex cooperatively guard T‐cell fate and inhibit OPA1‐mediated mitochondrial fusion in T cells
Liao R, Wu Y, Qin L, Jiang Z, Gou S, Zhou L, Hong Q, Li Y, Shi J, Yao Y, Lai L, Li Y, Liu P, Thiery JP, Qin D, Graf T, Liu X, Li P |
The EMBO Journal | 2023 |
|
Multi-objective optimization reveals time- and dose-dependent inflammatory cytokine-mediated regulation of human stem cell derived T-cell development
J Edgar, Y Michaels, P Zandstra |
npj Regenerative Medicine | 2022 |
|
Human induced-T-to-natural killer cells have potent anti-tumour activities
Z Jiang, L Qin, Y Tang, R Liao, J Shi, B He, S Li, D Zheng, Y Cui, Q Wu, Y Long, Y Yao, Z Wei, Q Hong, Y Wu, Y Mai, S Gou, X Li, R Weinkove, S Norton, W Luo, W Feng, H Zhou, Q Liu, J Chen, L Lai, X Chen, D Pei, T Graf, X Liu, Y Li, P Liu, Z Zhang, P Li |
Biomarker Research | 2022 |
|
Revolution of CAR Engineering For Next-Generation Immunotherapy In Solid Tumors.
Yu T, Yu SK, Xiang Y, Lu KH, Sun M |
Frontiers in immunology | 2022 |
|
Generation of T-cell-receptor-negative CD8αβ-positive CAR T cells from T cell-derived induced pluripotent stem cells
van der Stegen SJ, Lindenbergh PL, Petrovic RM, Xie H, Diop MP, Alexeeva V, Shi Y, Mansilla-Soto J, Hamieh M, Eyquem J, Cabriolu A, Wang X, Abujarour R, Lee T, Clarke R, Valamehr B, Themeli M, Riviere I, Sadelain M |
Nature Biomedical Engineering | 2022 |
|
BCL11B depletion induces the development of highly cytotoxic innate T cells out of IL-15 stimulated peripheral blood αβ CD8+ T cells
Forkel H, Grabarczyk P, Depke M, Troschke-Meurer S, Simm S, Hammer E, Michalik S, Hentschker C, Corleis B, Loyal L, Zumpe M, Siebert N, Dorhoi A, Thiel A, Lode H, Völker U, Schmidt CA |
OncoImmunology | 2022 |
|
Optimization of the proliferation and persistency of CAR T cells derived from human induced pluripotent stem cells.
Ueda T, Shiina S, Iriguchi S, Terakura S, Kawai Y, Kabai R, Sakamoto S, Watanabe A, Ohara K, Wang B, Xu H, Minagawa A, Hotta A, Woltjen K, Uemura Y, Kodama Y, Seno H, Nakatsura T, Tamada K, Kaneko S |
Nature Biomedical Engineering | 2022 |
|
Recent advances and discoveries in the mechanisms and functions of CAR T cells
RC Larson, MV Maus |
Nature Reviews Cancer | 2021 |
|
The role of the thymus in allogeneic bone marrow transplantation and the recovery of the peripheral T-cell compartment
E Velardi, E Clave, LC Arruda, F Benini, F Locatelli, A Toubert |
Seminars in Immunopathology | 2021 |
|
Sleeping Beauty-engineered CAR T cells achieve anti-leukemic activity without severe toxicities
Chiara F. Magnani, Giuseppe Gaipa, Federico Lussana, Daniela Belotti, Giuseppe Gritti, Sara Napolitano, Giada Matera, Benedetta Cabiati, Chiara Buracchi, Gianmaria Borleri, Grazia Fazio, Silvia Zaninelli, Sarah Tettamanti, Stefania Cesana, Valentina Colombo, Michele Quaroni, Giovanni Cazzaniga, Attilio Rovelli, Ettore Biagi, Stefania Galimberti, Andrea Calabria, Fabrizio Benedicenti, Eugenio Montini, Silvia Ferrari, Martino Introna, Adriana Balduzzi, Maria Grazia Valsecchi, Giuseppe Dastoli, Alessandro Rambaldi, Andrea Biondi |
Journal of Clinical Investigation | 2020 |
|
Chimeric Antigen Receptor (CAR)-Modified Immune Effector Cell Therapy for Acute Myeloid Leukemia (AML)
UH Acharya, RB Walter |
Cancers | 2020 |
|
Use of Cell and Genome Modification Technologies to Generate Improved “Off-the-Shelf” CAR T and CAR NK Cells
MA Morgan, H Büning, M Sauer, A Schambach |
Frontiers in immunology | 2020 |
|
Adding chimeric antigen receptor-induced killer cells to the medical oncology shelf
Brigett Brandjes, Marco Davila |
Journal of Clinical Investigation | 2019 |
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