Lipid Uptake via FATP2 Enhances CAR-T Therapy Resistance in B-cell Acute Lymphoblastic Leukemia

This study identifies Fatty Acid Transport Protein 2 (FATP2) as a critical metabolic vulnerability in relapsed/refractory B-ALL. FATP2-mediated free fatty acid uptake by TP53-mutant B-ALL blasts represent a potential leukemia-intrinsic mechanism of CAR-T resistance. Further, targeting FATP2-mediated exogenous lipid uptake represents a novel means of enhancing CD19-directed immunotherapy efficacy. CAR T or Mock T cells were co-cultured with isogenic 697 B-ALL cell lines at 1:16 E:T ratio in lipid-replete media supplementted with 4 U/mL human IL-2 for 72 h. For all CAR-T killing assays, target cells were seeded at a fixed cell surface density of 20,000 target cells (B-ALL) per 0.32 cm2.