CAR T
Published on April 24, 2025
Modulating abnormal CLL T-cell metabolism to boost CAR T-cell therapy
by Blood Advances
Gamal W, Goedhart NB, Simon-Molas H, et al. Mitigating T-Cell Mitochondrial Dysfunction in CLL to Augment CAR T-Cell Therapy: Evaluation in an Immunocompetent Model. Blood Advances. 2025; (doi: 10.1182/bloodadvances.2024014822).
Chimeric antigen receptor (CAR) T-cell treatments have suboptimal performance in the setting of chronic lymphocytic leukemia (CLL), but researchers have identified a potential pathway to increase efficacy. Based on the recent discovery that mitochondrial mass in CAR T cells influences CLL clinical outcomes, investigators turned their focus to the metabolic processes that support T-cell response. Integrated metabolic and functional analyses were conducted to assess the mitochondrial fitness in CLL T cells. Scientists observed an accumulation of impaired, depolarized mitochondria across all T-cell subsets in treatment-naive CLL patients, which worsened as the disease advanced. According to the study authors, the finding suggests that regulating this dysfunction in the CLL T-cell metabolism could boost the effects of CAR T and other autologous T-cell interventions. Results from an immunocompetent mouse model support the theory, with ex vivo programming of CLL T-cell mitochondrial activity improving CAR T-cell efficacy and persistence.
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