Fig. 6: HA-GD2 CAR T cells require higher BACH2 quantity to overcome exhaustion.

a, Schematic of tonic signal strength induced by CD22 or HA-GD2 CARs. b, Co-expression of TIM3 and LAG3 by CAR T cells at the end of manufacture. c, CAR T cell expansion over time during chronic stimulation with the GD2⁺ neuroblastoma cell line SY5Y. d–f, Central memory (d), effector memory (e) and terminal effector (f) composition of CAR T cells over time during chronic stimulation. g, Co-expression of CD39 and PD1 in CAR T cells over time. Representative data are from n = 3 donors. h, Control of in vivo neuroblastoma. i, Percentage change in weight of mice over time after treatment with CAR T cells 30 d after engraftment. Boxes represent minima and maxima with the line at the mean. j–l, Total nucleated cells in the spleen (j), fraction of CAR⁺ T cells in the spleen (k) and memory composition of CAR⁺ T cells in the spleen (l). For h–l, there are n = 8 mice per group except for the NTD control (n = 5). All data are presented as either individual values or mean values ± s.e.m. *P < 0.05, P < 0.01, P < 0.001, P < 0.0001 by two-way ANOVA with Bonferroni’s adjustment for multiple comparisons. NSG, NOD-SCID-γc^−/− mice. Schematic in a created with BioRender.com.