Manipulation of FOXO3 affects 41BB-based CAR T-cell function. (A) Representation of FOXO3^KO cells being evaluated. (B) Target Nalm6 cells per CAR T cells over the course of chronic stimulation. Representative data from n = 3 donors. (C) Day of dysfunction onset as measured based on the first day of T-cell contraction or loss of tumor control. Data from n = 3 independent donors. (D) Representation of FOXO3^OE cells being evaluated. (E) Target Nalm6 cells per CAR T cells over the course of chronic stimulation. Representative data from n = 3 donors. (F) Day of dysfunction onset as measured by first day of T-cell contraction or loss of tumor control. Data from n = 3 independent donors. (G) Survival of mice after treatment with 0.125 × 10⁶ CAR T cells. Significance determined using log-rank test. (H) Survival of mice after treatment with 0.5 × 10⁶ CAR T cells. Significance determined using log-rank test. For both experiments n = 5 mice per group. ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. ns, not significant.