Fig. 4. CD3γ and CD3δ ICDs protect CAR T cells from dysregulation on serial antigen encounters.
a, UMAP plot from CyTOF data showing all the samples together (left), pooled nonchallenged or rechallenged cells (middle) and cells sorted by CAR (right). b,c, Percentage of cells expressing T cell exhaustion/dysregulation markers (b) and cytokine production (c) comparing all nonchallenged samples pooled with all rechallenged samples pooled. d, Heatmap showing the cytokine production in nonchallenged and rechallenged conditions. e, Cytokine secretion assayed by ELISA of CAR T cells on incubation with Nalm6 cells (1:1 ratio) for 24 h after one (black) or three (white) challenges. Each dot represents an independent donor (n = 4). f, Specific killing of CD19+ Nalm6 cells by CAR T cells submitted to repetitive stimulations (E:T ratio = 1:1 for 6–8 h). Each dot represents an independent donor (n = 3 for a–d, n = 4 for e, n = 5 for f). Data are represented as mean ± s.d. Wilcoxon’s two-tailed test (b and c), two-way ANOVA followed by Sidak’s multiple-comparison test (e) or one-way ANOVA followed by Dunnett’s multiple-comparison test (f) is used.