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| Status |
Public on Mar 27, 2019 |
| Title |
CAR T cell trogocytosis and cooperative killing regulate tumour antigen escape |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Chimeric antigen receptors (CARs) are synthetic receptors for antigen that reprogram T cell specificity, function and persistence. Patient-derived CAR T cells have demonstrated remarkable efficacy against a range of B-cell malignancies, and early trial results suggest activity in multiple myeloma. Despite high complete response rates, relapses occur in a large fraction of patients, some of which are antigen-negative and others antigen-low. Unlike mechanisms resulting in complete and permanent antigen loss, those leading to antigen-low tumour escape remain obscure. In murine leukaemia models, we show that CARs provoke reversible antigen loss through trogocytosis, an active process whereby target antigen is transferred to T cells, thereby decreasing target density on tumour cells and abating T cell activity by promoting fratricide killing and exhaustion. These mechanisms affect both CD28 and 4-1BB-based CARs, albeit differentially, depending on antigen density. They can be offset by cooperative killing and combinatorial targeting.
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| |
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| Overall design |
Examination of mRNA CD19 expression in NALM6 retrieved from relapsed mice treated with 19-BBζ CAR T cells (D0), retrieved NALM6 after ex-vivo culture (D6), and NALM6 culture in vitro (ctrl).
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| |
|
| Contributor(s) |
Hamieh M, Sadelain M |
| Citation(s) |
30918399 |
| |
| Submission date |
Feb 19, 2019 |
| Last update date |
Apr 02, 2019 |
| Contact name |
Yu-Jui Ho |
| E-mail(s) |
hoy@mskcc.org
|
| Organization name |
Memorial Sloan Kettering Cancer Center
|
| Department |
Cancer Biology & Genetics Program
|
| Street address |
417 E 68th St
|
| City |
New York |
| State/province |
New York |
| ZIP/Postal code |
10065 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (17)
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| Relations |
| BioProject |
PRJNA523212 |
| SRA |
SRP186290 |
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