1. CAR expression promotes tonic activation of signaling networks.
CAR expression promotes tonic activation of signaling networks. (A) Mass cytometry analysis of baseline phosphoprotein abundance in expanded CD8+ T cells transduced to express the CD19-28ζ CAR as indicated. Histograms are representative of three independent donors. (B) Mass cytometry analysis of baseline phosphoprotein abundance in CD4+ (green), CD8+ (blue), and Vδ2+ (yellow) T cells transduced to express the CD19-28ζ CAR. Correlation of EMD score with transduction efficiency is from analysis of at least three independent donors. (C and D) Mass cytometry analysis of phosphoprotein abundance in expanded T cells transduced with CD19-28ζ stimulated with antibodies against CD3 (blue), CD28 (green), CD3+CD28 (red), or CAR (violet). Correlation of EMD scores in untransduced and CAR-transduced cells (C) and EMD scores for pSLP-76, pERK, and pMAPKAPK2 (D) are means ± SEM of at least three independent donors. (E) Flow cytometry analysis of TIM-3 and PD-1 abundance on T cells expressing a CD19-28ζ, GD2-28ζ (huk666), or GD2-28ζ (14G2A) CAR. Data are means ± SEM pooled from at least four biological replicates (see also fig. S11). Pearson correlation (B) and analysis of covariance (ANCOVA) (C) P values are displayed; (D) *P < 0.05, **P < 0.01 by paired t test. ns, not significant.
Jonathan Fisher et al., Sci. Signal. 2019;12:eaax1872
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