GLUT1 overexpression in CAR-T cells induces metabolic reprogramming and enhances potency.

ABSTRACT: The intensive nutrient requirements needed to sustain T cell activation and proliferation, combined with competition for nutrients within the tumor microenvironment, raise the prospect that glucose availability may limit CAR-T cell function. Here, we seek to test the hypothesis that stable overexpression (OE) of the glucose transporter GLUT1 in primary human CAR-T cells would improve their function and antitumor potency. We observe that GLUT1OE in CAR-T cells increases glucose consumption, glycolysis, glycolytic reserve, and oxidative phosphorylation, and these effects are associated with decreased T cell exhaustion and increased Th₁₇ differentiation. GLUT1OE also induces broad metabolic reprogramming associated with increased glutathione-mediated resistance to reactive oxygen s

SUBMITTER: Guerrero JA 

PROVIDER: S-EPMC11456602 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature