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Solute carrier family 2, facilitated glucose transporter member 3 (GLUT3) is a high-affinity glucose transporter that plays a pivotal role in cellular energy metabolism by facilitating the uptake of glucose [1]. In the field of adoptive cell therapy, specifically Chimeric Antigen Receptor (CAR) T-cell therapy, GLUT3 is targeted for overexpression to enhance the metabolic fitness of T cells within the immunosuppressive and nutrient-deprived tumor microenvironment (TME) [2]. Because cancer cells aggressively consume glucose (the Warburg effect), CAR-T cells often face metabolic starvation, leading to reduced effector function and exhaustion. GLUT3 possesses a higher affinity for glucose (lower Michaelis constant, Km) than the more common GLUT1, allowing engineered CAR-T cells to maintain glycolytic flux even when glucose levels are critically low [3]. This metabolic reprogramming is designed to improve the persistence and anti-tumor efficacy of CAR-T cells against solid tumors [2, 3]. While primarily a research-stage strategy, modulating GLUT3 represents a significant frontier in overcoming the metabolic barriers to successful immunotherapy [4]. References: [1] UniProt (P11169); [2] Cretenet, G., et al. (2016) PubMed: 27125739; [3] Kouidhi, S., et al. (2018) Frontiers in Immunology; [4] Chang, C. H., et al. (2015) Cell.
Facilitated diffusion of glucose across the plasma membrane down its concentration gradient, providing the necessary substrate for glycolysis and cellular energy production [1].
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