Extended Data Fig. 6: In vivo T cell exhaustion of TRAC-1928ζ mutants compared to wild-type TRAC-1928ζ.
From: Calibration of CAR activation potential directs alternative T cell fates and therapeutic potency
a, NALM6-bearing mice were treated with 1 × 105 CAR T cells and euthanized at day 17 after infusion. FACS analysis of expression of exhaustion markers on CAR+ T cells, representative of n = 5 mice per group in one independent experiment. b–g, NALM6-bearing mice were treated with 1 × 105 TRAC-edited naive T cells. 16 (b–c) and 36 (e,g) d after CAR administration, TRAC-1928ζ and TRAC-1XX cells from bone marrow and spleen were exposed to ex vivo stimulation with NALM6 or PMA/Ionomycin (Iono). Cytokine and granzyme B (GrB)/ CD107a expression on CAR T cells as demonstrated by percentage of expression and flow cytometric analyses, representative for n = 3 mice in two independent experiments (b) and for n = 3 replicates (g). Expression of exhaustion markers PD1+LAG3+ on CAR T cells (d) and cytotoxic activity (f) of TRAC-1XX (day 36) after 10 h of co-culture with NALM6. All data are means ± s.e.m., n = 3 mice per group
