Fig. 7: Pharmacological LSD1 inhibition enhances the antitumor potency of human CAR T cells.

Flow cytometry analysis of cytokine production (a) and multiple-cytokine producers (b) in human peripheral CD8⁺ T cells activated and expanded in vitro for 10 days with or without GSK treatment (n = 9 donors). c Flow cytometry analysis of GzmB and Ki-67 expression in GSK- or Veh-treated human CD8⁺ T cells (n = 6 donors). d Flow cytometry analysis of FMC63-scFv and EGFP expression in human CD8⁺ T cells transduced with a lentiviral plasmid encoding CD19-CAR and EGFP and treated with or without GSK. Cytotoxicity of GSK- or Veh-treated CD19-CAR T cells or unmodified mock T cells in tumor killing assays using CD19⁺ Nalm6-lucif-EGFP (e, f) or Raji (g) cells as targets and single-stimulated (e) or repeatedly stimulated (f, g) CD19-CAR T cells as effectors (n = 3 for e and g, and n = 4 for f). Representative bioluminescence images (h), quantitative bioluminescence imaging data (i), and survival curves (j) of NCG mice intravenously injected with 10⁶ Nalm6-lucif-EGFP cells and infused with 2 × 10⁵ CD19-CAR or mock T cells 7 days later (n = 5 mice per group). Representative flow plots (k), frequencies (l), and cell numbers (m) of human mock CD8⁺ T cells and GSK- or Veh-primed CD19-CAR CD8⁺ T cells in peripheral blood of NCG recipient mice on day 12 post transfer (n = 4 mice for mock T and CAR T Veh, and n = 3 mice for CAR T GSK). n Tumor growth curves of NCG mice subcutaneously injected with 10⁶ A375-CD19 cells and infused with 2 × 10⁵ CD19-CAR T or mock T cells 8 days later (n = 5 mice per group). Data are pooled from three independent experiments (a–c) or represent two independent experiments (d–m) and are presented as mean ± SD (e–g) or mean ± SEM (l–n). Statistical significance was determined by paired t-test (a, c), two-sided unpaired t-test (e–g, l, m), two-way ANOVA (n), or log-rank test (j). Source data are provided as a Source Data file.