PI3Kδ inhibition allows for persistent CAR T cells in CLL in vivo. (A) Experimental design for the generation and ex vivo reprogramming of AT Eμ-TCL1 CAR T cells using idelalisib (idela), followed by infusion into different groups of AT Eμ-TCL1 mice with established disease. (B) Percentages of GFP⁺ CAR T cells (of total T cells) in peripheral blood (PB) for 7 weeks since the start of CLL AT in mice (arrow pointing to the time point when cyclophosphamide [CTX] and CAR T cells were injected). (C) Representative dot plots showing gating on CD19⁺ B cells and CD3⁺ T cells, alongside quantification of absolute CLL cell (CD19⁺CD5⁺B220^lo) counts in PB. (D) Kaplan-Meier survival analysis of CAR T-cell–treated mice compared with control mice receiving untransduced (UT) T cells. (E) Spleen analysis 4 weeks after CAR T-cell injection, showing representative spleen sizes and tabulated weights, absolute CLL cell counts, and GFP⁺ CAR T-cell counts. (F) Quantitative results of endogenous T-cell memory phenotypes in the spleens of treated mice (naïve, CD44^–CD62L⁺; CM, CD44⁺CD62L⁺; EM, CD44⁺CD62L^–; and effector, CD44^–CD62L). (G) Bone marrow (BM) analysis 4 weeks after CAR T-cell injection, showing absolute CLL cell counts and GFP⁺ CAR T-cell counts. The experiments included 12 mice for the idela CAR T-cell group, 11 mice for the DMSO CAR T-cell group, and 9 mice for the UT control group. On week 4 after CAR T-cell infusion, 3 randomly selected mice from each group were euthanized for spleen and BM analyses. Data are representative of 2 independent experiments. Each symbol represents an individual animal. Data are presented as mean ± SD. Differences analyzed using an ordinary 1-way ANOVA with Tukey multiple correction test in panels B-C,E-G. Log-rank (Mantel-Cox) test was used for survival study comparisons. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. Panel A was created with BioRender.com. AT, adoptive transfer; GFP, green fluorescent protein; ns, non-significant; Untransd, untransduced.