한빛사논문
- 조회380
Aliya Lakhani 1, Ximin Chen 1, Laurence C. Chen 1, Mihe Hong 1, Mobina Khericha 2, Yu Chen 3, Yvonne Y. Chen 1,2,4,5 & Junyoung O. Park 1,4,*
1Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA, USA.
2Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
3Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, USA.
4Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, CA, USA.
5Parker Institute for Cancer Immunotherapy at UCLA, Los Angeles, CA, USA.
*Corresponding author: correspondence to Junyoung O. Park
Abstract
Metabolism is an indispensable part of T cell proliferation, activation and exhaustion, yet the metabolism of chimeric antigen receptor (CAR)-T cells remains incompletely understood. CARs are composed of extracellular domains—often single-chain variable fragments (scFvs)—that determine ligand specificity and intracellular domains that trigger signalling following antigen binding. Here, we show that CARs differing only in the scFv variously reprogramme T cell metabolism. Even without exposure to antigens, some CARs increase proliferation and nutrient uptake in T cells. Using stable isotope tracers and mass spectrometry, we observed basal metabolic fluxes through glycolysis doubling and amino acid uptake overtaking anaplerosis in CAR-T cells harbouring a rituximab scFv, unlike other similar anti-CD20 scFvs. Disparate rituximab and 14G2a-based anti-GD2 CAR-T cells are similarly hypermetabolic and channel excess nutrients to nitrogen overflow metabolism. Modest overflow metabolism of CAR-T cells and metabolic compatibility between cancer cells and CAR-T cells are identified as features of efficacious CAR-T cell therapy.
논문정보
- Research article
- 2024년 04월 (BRIC 등록일 2024-04-29)
- 국외 연구진
- 생명과학 > 생화학
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