Figure 6.
Figure 6. Increased mitochondrial mass in CAR T cells from CLL patients showing complete response to CD19 CAR T-cell therapy. Patients were separated into 2 groups based on response to therapy: CRs and NRs. Viably frozen infusion products from CLL patients undergoing a CD19 CAR T-cell trial (NCT01747486, and NCT01029366; CR, n = 7; NR, n = 20) were thawed and CAR+CD8+ T cells were analyzed for (A) mitochondrial mass (Mitotracker Green), glucose uptake (2-NBDG), mitochondrial membrane potential (Mitotracker Orange), and mitochondrial ROS (MitoSOX). (B) Mitochondrial mass of CAR+CD8+ T cells plotted against determinants of clinical outcome including expansion of the CAR T-cell culture (fold expansion), expansion of the CAR T cells after infusion (qPCR CAR days 0-35), persistence of CAR T cells calculated at days 0 to 35 postinfusion (AUC days 0-35), and overall expansion of CD8+ T cells after infusion (CD3+CD8+ peak days 0-28) (CR, n = 6; NR, n = 18). (C) Mitochondrial mass of CAR+CD8+ T cells plotted against the percentage of CD27+ cells negative for PD-1, TIM-3, and LAG-3 (CR, n = 6; NR, n = 18). Normality was determined by a D’Agostino and Pearson normality test. The P value was calculated by a Mann-Whitney test (A). Correlations were determined by a Spearman Rho test (B-C). Data are presented as mean plus or minus SEM. *P < .05.

Increased mitochondrial mass in CAR T cells from CLL patients showing complete response to CD19 CAR T-cell therapy. Patients were separated into 2 groups based on response to therapy: CRs and NRs. Viably frozen infusion products from CLL patients undergoing a CD19 CAR T-cell trial (NCT01747486, and NCT01029366; CR, n = 7; NR, n = 20) were thawed and CAR+CD8+ T cells were analyzed for (A) mitochondrial mass (Mitotracker Green), glucose uptake (2-NBDG), mitochondrial membrane potential (Mitotracker Orange), and mitochondrial ROS (MitoSOX). (B) Mitochondrial mass of CAR+CD8+ T cells plotted against determinants of clinical outcome including expansion of the CAR T-cell culture (fold expansion), expansion of the CAR T cells after infusion (qPCR CAR days 0-35), persistence of CAR T cells calculated at days 0 to 35 postinfusion (AUC days 0-35), and overall expansion of CD8+ T cells after infusion (CD3+CD8+ peak days 0-28) (CR, n = 6; NR, n = 18). (C) Mitochondrial mass of CAR+CD8+ T cells plotted against the percentage of CD27+ cells negative for PD-1, TIM-3, and LAG-3 (CR, n = 6; NR, n = 18). Normality was determined by a D’Agostino and Pearson normality test. The P value was calculated by a Mann-Whitney test (A). Correlations were determined by a Spearman Rho test (B-C). Data are presented as mean plus or minus SEM. *P < .05.

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