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Status |
Public on Dec 31, 2019 |
Title |
Chimeric Antigen Receptor-Induced Bcl11b Suppression Propagates Natural Killer-Like Cell Development |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
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 suppresses Bcl11b, leading to suppression of T cell-associated gene expression and acquisition of natural killer (NK) cell-like properties. These results give important insights into differentiation of murine and human lymphoid progenitors driven by synthetic CAR transgene-expression and inform the potential use of ex vivo generated CARiK cells as a broadly applicable product for targeted immunotherapy.
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Overall design |
Microarray data analysis of sorted human CAR-engineered lymphoid progenitors (h1928z3: n=3; h19delta: n= 5; h1928z3 + hCD19: n= 3) from OP9-DL1 in vitro cultures on day 18. Human CD34+ HSPCs derived from umbilical cord blood samples were engineered with a CD28-based second-generation human CAR targeting human CD19 (h1928z3) or a non-signaling control CAR (h19delta) and pre-differentiated on OP9-DL1 stromal cells in vitro. For CAR stimulation, irradiated CD19+ Daudi cells were added during the culture (h1928z3_stim).
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Contributor(s) |
Maluski M, Sauer MG, Geffers R |
Citation(s) |
31479431 |
Submission date |
Jul 29, 2019 |
Last update date |
Apr 10, 2020 |
Contact name |
Robert Geffers |
E-mail(s) |
robert.geffers@helmholtz-hzi.de
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Phone |
+49 531-6181-3058
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Organization name |
HCI - Helmholtz Centre for Infection Research
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Department |
Dep. Molecular Bacteriology
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Lab |
Genome Analytics
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Street address |
Inhoffenstr. 7
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City |
Braunschweig |
ZIP/Postal code |
38124 |
Country |
Germany |
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Platforms (1) |
GPL23159 |
[Clariom_S_Human] Affymetrix Clariom S Assay, Human (Includes Pico Assay) |
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Samples (11)
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Relations |
BioProject |
PRJNA557165 |