Modulating CAR-T cell exhaustion and fitness in acute myeloid leukemia: mechanistic metabolic and microenvironmental strategies

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CAR T-cell therapy shows limited efficacy in acute myeloid leukemia (AML) due to antigenic heterogeneity and a suppressive microenvironment.
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Exhaustion in CAR T-cells is driven by transcriptional, epigenetic, metabolic, and functional dysfunction in the context of AML.
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The quality of autologous T cells from AML patients is often poor, impacting CAR T-cell manufacturing and effectiveness.
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Emerging strategies include multi-antigen approaches and next-generation CAR designs to improve specificity and safety in AML.
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Integrating manufacturing, metabolic interventions, and microenvironmental modulation is essential for enhancing CAR T-cell fitness in AML.

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