Extended Data Fig. 7: Dual-CAR T cells eliminate cognate targets and promote antigen-negative escape of leukaemia mixture with high antigen heterogeneity.
From: Leucine zipper-based immunomagnetic purification of CAR T cells displaying multiple receptors
a, C1498 acute myeloid leukaemia cell line was modified to singly express murine CD19, CD20, CD79bΔ (CD79b extracellular ___domain fused to CD28TM and CD3ζΔ; to promote surface expression without requiring CD79a coexpression), and BAFF-R. C1498 also was modified to express CBR, hCD8, and puroR. b–e, Albino B6 mice were sublethally irradiated and injected with either 1:1 mixture of C1498-CD19 and C1498-CD20 or a 1:1:1:1 mixture of C1498-CD19, C1498-CD20, C1498-CD79b, and C1498-BAFF-R and treated with dasatinib-cultured Zip-sorted dual-CAR 1XX T cells or left untreated. b, Leukaemia BLI from single experiment. Log-transformed BLI AUC values were compared using a Vardi test with FDR correction. c, Survival. Differences in survival were compared with a log-rank test. d, Target antigen expression of representative C1498 leukaemia harvested from bone marrow at time of euthanasia for leukaemia progression. Gated on hCD8+ C1498. e, Target antigen expression on bone marrow leukaemia obtained from mice reaching humane endpoints. Percentage CD20+ C1498 fraction of total bone marrow C1498 was compared with two-tailed t-test. Data are mean ± SEM of biological replicates.
