Table 2.

Metabolic genetic alterations in CAR T cells to improve their function and T-cell fate

Target	Genetic modification	Effect on metabolism	Effect on T-cell fate	Ref.
Fumarase	Overexpression	↓ Fumarate levels	↑ CAR T-cell function	[150]
Regnase-1	Knock out	↑ Mitochondrial mass and volume ↑ ΔΨM	↑ TCF1 expression, ↑ Memory T cells	[163–165]
PRODH2	Overexpression	↑ Number of mitochondria ↑ Mitochondria granula ↑OXPHOS	↑ Effector function ↑ Memory T cells	[166]
Argininosuccinate synthase (ASS)	Overexpression	↑ Arginine resynthesis	↑ In vivo anti-tumor efficacy ↓ Exhaustion	[168]
Ornithine transcarbamylase (OTC).	Overexpression	↑ Arginine resynthesis	↑ In vivo anti-tumor efficacy ↓ Exhaustion	[168]
SLC7A5/SLC7A11	Overexpression	↑ Amino acid uptake ↑ Intracellular arginase expression and activity	↑ CAR T-cell proliferation under low tryptophan or cystine conditions	[169]
Arginase	Overexpression	↑Arginine catabolism	↑ CAR T-cell proliferation ↑ In vivo anti-tumor efficacy	[169]
Kynureninase	Overexpression	↑ Kynunerine catabolism	↑ Killing ↑ Memory formation	[170]