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This article explores how reprogramming glutamine metabolism enhances the function and efficacy of BCMA-targeted CAR T-cell therapies in multiple myeloma (MM). Key findings include: 1) Glutamine deprivation hampers CAR T-cell proliferation and functionality; 2) Overexpression of the glutamine transporter Asct2 in CAR T-cells restores proliferation, IFN-γ production, and cytotoxicity in glutamine-poor environments; 3) Asct2 expression reprograms CAR T-cell metabolic fitness by upregulating mTORC1 signaling and improving mitochondrial and glycolytic functions; 4) Enhanced metabolic fitness translates into improved therapeutic efficacy and survival in murine MM models; 5) In patients, low MM cell Asct2 expression correlates with poorer outcomes from BCMA-CAR T and immunotherapy.
