Extended Data Fig. 7: Inhibitor of p38 kinase increases the efficacy of CAR T cell therapies.
From: Targeting PARP11 to avert immunosuppression and improve CAR T therapy in solid tumors
a Representative flow cytometry analysis of CAR expression in human T cells after Meso–BBz transduction and treatment with vehicle or p38 inhibitor Ralimetinib (LY2228820, LY, 5 μM, 72 h). b Flow cytometry analysis of levels of IFNAR1 on the surface of Meso–BBz CAR T cells pretreated with indicated inhibitors (LY2228820, LY, 5 μM, 72 h) and then treated by adenosine (Ado, 1 mM) for 24 h. Data are shown as mean ± SEM (n = 4 independently treated cell cultures). Statistical analysis was performed using ordinary one-way ANOVA with Tukey’s multiple comparisons test. ****P < 0.0001. c Lysis of EM-Meso-GFP-Luc cells by Meso–BBz CAR T pretreated with inhibitors (LY2228820, LY, 5 μM, 72 h) at indicated conditions (E: T = 10:1). Data are shown as mean ± SEM (Veh treated with or without Ado, n = 5 co-cultures; LY treated with or without Ado, n = 5 co-cultures.). Statistical analysis was performed using ordinary one-way ANOVA with Tukey’s multiple comparisons test. **P < 0.0056. d Tumor growth of NSG mice that were injected s.c. with 1 × 106 EM-Meso-GFP-Luc cells. Mice were i.v. treated with 2 × 106 BBZ-SS1 CAR T cells on day 7. BBZ-SS1 CAR T cells were pretreated with LY (5 μM) or Veh for 72 h before injected to mice. Data are shown as mean ± SEM (Control, n = 7 mice; BBZ-SS1, n = 9 mice; BBZ-SS1 + LY, n = 10 mice). Statistical analysis was performed using two-way ANOVA with Tukey’s multiple comparisons test. ****P < 0.0001. e The Kaplan-Meier analysis of survival of animals from experiment described in Extended Data Fig. 7d (n = 5 mice for each group). Statistical analysis was performed using Gehan-Breslow-Wilcoxon test.
