Metabolic armouring of CAR and TCR T cells
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Cancer immune therapy with engineered immune cells is standard of care in certain hematologic malignancies. However, solid tumor outcomes in clinical trials are lagging significantly behind. Engineered T cells face a myriad of challenges within the tumor microenvironment, one of which is competition for metabolites and a carbon source for adenosine triphosphate generation. Glucose is the main source of carbon for cellular metabolism, and it is critically limited in the microenvironment of solid tumors due to poor vascularization and competition with tumor cells for uptake. Here, we aimed to overcome this limitation by equipping T cells with the capability to use an alternative carbon source. We demonstrate that fructose can act as an alternative carbon source for T cells modified with chimeric antigen receptors or T cell receptors and the expression of glucose transporter 5. This simple manipulation is highly compatible with clinical development approaches to optimize cell therapy outcomes.
