Fig. 8.

IFN gene therapy boosts activation of adoptively transferred CAR19-transduced T cells and enhances survival. a, b Experimental design (a) and ALL growth over time (b, absolute numbers in PB; mean ± SEM) in CTRL + CTRLT (n = 5), IFN + CTRLT (n = 5), CTRL + CART19 (n = 7), IFN + CART19 (n = 7). ****p < 0.0001, nonparametric rank-based method for longitudinal data in factorial experiments. c Percentage (mean ± SEM) of Lag3 expression on CD8 + NGFR + CART19 cells in the PB of mice from b. Long-term surviving mice are shown in green. Each line represents a mouse. d, e Experimental design (d) and ALL growth over time (e, absolute numbers in PB; mean ± SEM) in CTRL + CTRLT (n = 7), IFN + CTRLT (n = 6), CTRL + CART19 (n = 7), IFN + CART19 (n = 6), CTRL + iCART19 (n = 7), IFN + iCART19 (n = 6), IFN + CTRLT late (n = 6, late intervention trial), IFN + iCART19 late (n = 6, late intervention trial). ****p < 0.0001, nonparametric rank-based method for longitudinal data in factorial experiments. Statistical analysis is performed on selected groups (see Supplementary Tables 9 and 10). f Percentage overtime (mean ± SEM) of Lag3 expression on CD8 + NGFR + CART19 cells in the PB of mice from b. CTRL + CART19 and CTRL + iCART19 mice are plotted together. Long-term surviving mice are shown in green. Each line represents a mouse. g Survival curve of mice treated with CART19 or iCART19 cells from b, e. CTRL mice treated with CART19 and iCART19 from b, e are plotted together (CTRL + i/CART19, n = 21), IFN + CART19 (n = 13), IFN + iCART19 (n = 6), IFN + iCART19 late (n = 6). ****p ≤ 0.0001, Mantel–Haenszel test, adjusted by Bonferroni method