Figure 3. Metabolic bolstering of T cells to better withstand the TME.

Instead of altering the TME, T cells used for cellular therapies (CAR T cells or adoptive cell therapy) can be metabolically bolstered before patient reinfusion. During the in vitro expansion phase of cellular therapies, limiting metabolites such as glucose, glutamine, or oxygen in the media or using a medium with physiologic metabolite concentrations may better prepare T cells for survival and efficacy in the metabolically harsh TME. Alternatively, T cells can be engineered to either overexpress key metabolic genes, such as PGC1a, to improve mitochondrial fitness, or delete metabolic regulators such as regnase-1, which negatively regulates mitochondrial fitness, to give T cells a metabolic edge within the TME.