Determining and combating the effects of lactic acid on CAR T cells

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Lactic acid is a metabolite generated from pyruvate the end-product of glycolysis and glutaminolysis. It is abundant in tumours, as tumour cells typically demonstrate elevated glycolytic activity and decreased citric acid cycle activity. Lactate can be utilised by some cells as a carbon source for catabolism and ATP generation but lactic acid appears to be antagonistic to effector T cells. Lactic acid is therefore anticipated to diminish the potency of CAR T cells in tumours. This will establish models to dissect the antagonistic effects of lactic acid on CAR T cells and to evaluate strategies to counteract them.