Fig. 3: Overexpression of FOXO1 enhances CAR T cell persistence and antitumour activity against leukaemia in a TCF7-independent manner.

a, Subcurative doses of 0.1 × 10⁶–0.2 × 10⁶ tNGFR⁺ CD19.28ζ cells were infused into Nalm6-bearing mice seven days after engraftment. Schematic (top) and survival curve (bottom) are shown; n = 9-10 mice per group. b–d, Curative doses of 1 × 10⁶ tNGFR⁺ CD19.28ζ cells were infused into Nalm6-bearing mice seven days after engraftment. Mice were rechallenged with 10 × 10⁶ CD19⁺ or CD19⁻ Nalm6 on day 21 after CAR T cell infusion (n = 2 donors tested in 2 independent experiments). b, Rechallenge Nalm6 model. Schematic (top) and quantification (bottom) of circulating human CD45⁺ CAR T cells. Mean ± s.e.m. of n = 3–7 mice per group from one representative donor. c, Survival curve after rechallenge (n = 3–8 mice per group pooled from 2 donors). d–f, CD19.28ζ cells overexpressing tNGFR or FOXO1_OE were gene-edited to knock out AAVS1 (control; AAVS1) or TCF7 (TCF7_KO). d, RNA-seq PCA. e, Volcano plots of DEGs; n = 3 donors (Bonferroni-adjusted P < 0.05 with abs(logFC) > 0.5). f, Stress test Nalm6 model. tNGFR⁺ CD19.28ζ cells (0.6 × 10⁶ cells) were infused into Nalm6-bearing mice seven days after engraftment. Survival curve is shown (n = 8–10 mice per group). a,c,f show pooled data from two donors tested in two independent experiments. Statistical comparisons were performed using log-rank Mantel–Cox test (a,c,f) and DESeq2 (e). NS, not significant.

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