Fig. 1. Loss of SPPL3 results in resistance to CD19-directed CAR T cells.

a Schematic of the genome-wide knockout screen in Nalm6 ALL. b Plot of MAGeCK beta scores for genes that were enriched in CART19 targeted cells compared to untargeted T cells. c Survival of Nalm6 and d OCI-Ly10 over time after combination with CART19 (E:T ratio 0.25:1). e Tumor radiance over time and f Survival of NSG mice treated engrafted with either WT or SPPL3^KO Nalm6 after treatment with CART19 cells (n = 7 per group) or no treatment (n = 4 per group). ***P < 0.001, **** Error bars reflect mean ± standard error of the mean (s.e.m.). P < 0.0001 by two-way ANOVA with Bonferroni correction for multiple comparisons. Survival analyses were performed with the log-rank test. Data were representative of n = 5 (c, d) individual experiments with distinct donor T cells. In c statistical annotations reflect differences between WT and SPPL3^KO clone 1 (upper) and WT and SPPL3^KO clone 2 (lower). Source Data are provided as a Source Data file.