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| Status |
Public on May 30, 2024 |
| Title |
GLUT1 overexpression enhances CAR T cell metabolic fitness and anti-tumor efficacy |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The tumor microenvironment presents many obstacles to effective CAR T cell therapy, including glucose competition from tumor and myeloid cells. Using mouse models of acute lymphoblastic leukemia (ALL), renal cell carcinoma (RCC), and glioblastoma (GBM), we show that enforced expression of the glucose transporter GLUT1 enhances anti-tumor efficacy and promotes favorable CAR T cell phenotypes for two clinically relevant CAR designs, 19-28z and IL13Ra2-BBz. In the NALM6 ALL model, 19-28z-GLUT1 promotes Tscm formation and prolongs survival. RNA sequencing of these CAR T cells reveals that overexpression of GLUT1, but not GLUT3, enriches for genes involved in glycolysis, mitochondrial respiration, and memory precursor phenotypes. Extending these data, 19-28z-GLUT1 CAR T cells improve tumor control and response to rechallenge in an RCC patient derived xenograft model. Furthermore, IL13Ra2-BBz CAR T cells overexpressing GLUT1 prolong survival of mice bearing orthotopic GBMs and exhibit decreased exhaustion markers. This novel engineering approach can offer a competitive advantage to CAR T cells in harsh tumor environments where glucose is limiting.
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| Overall design |
To understand what led to the improved anti-tumor efficacy of 19-28z-GLUT1 CAR T cells, we performed SMARTer-RNA-seq on flow-sorted CAR T cells from bone marrow at 7 days after CAR T cell infusion
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| Contributor(s) |
Shi Y, Kotchetkov IS |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Apr 25, 2024 |
| Last update date |
May 30, 2024 |
| Contact name |
Yuzhe Shi |
| E-mail(s) |
shiy3@mskcc.org
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| Organization name |
Memorial Sloan Kettering Cancer Center
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| Department |
Immunolgy
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| Lab |
Sadelain Lab
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| Street address |
1250 First Avenue
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA1104654 |
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