Fig. 3: Correlative assessment of CAR-T persistence and patient cytokine profiles.
a, Expression of CD4, CD27, CD62L and CCR7 on Tcm- and Tn/mem-derived CAR + T cell products (n = 58 cell products) as determined by flow cytometry, with means (± standard error of the mean) indicated by black bars. ****P < 0.0001; ***P ≤ 0.0005 using a two-sided unpaired t-test. b, Box-and-whisker plot of maximum WPRE copy number per microgram of PBMC DNA by arm (n = 2, 17, 10, 8 and 20, respectively, for arms 1–5; reference Extended Data Fig. 4e). The median and interquartile range with whiskers extending to the minimum and maximum values are depicted. *P = 0.075, **P ≤ 0.003 and ***P ≤ 0.0003 when using a two-sided t-test. Legend indicates maximum infusion dose per dose schedule (×106). c, Low-dimensional representations of cytokine measurements colored by compartment (SER, CSF or TCF), day of any given cycle (up to six cycles, with CXD0 being day 0 of cycles 2–6), cycle number, delivery route or dose (legend indicates maximum infusion dose × 106). d, Heatmap of cytokine levels across cycles (C1–6), preinfusion (D0) and postinfusion (D1) in either the CSF (left), TCF (middle) or serum (right), with the median log10 fold change from baseline (C1D0) shown. e, Box-and-whisker plot of the change in IFNγ pathway score (log10(IFNγ) + log10(CXCL9) + log10(CXCL10)) from baseline (C1D0) to the corresponding CXD1 within the CSF for survival evaluable patients treated on either arm 3, 4 or 5, for the first three cycles (at C1, n = 6, 5 or 14, respectively; at C2, n = 6, 6 or 15, respectively; at C3, n = 8, 5 or 16, respectively). The median and interquartile range with whiskers extending to the minimum and maximum values are depicted. Dose schedule (DS) is indicated by dot size; **P ≤ 0.0006 compared to each of the other arms using ANOVA. f, CSF IFNγ pathway score at C1D1 (log10(IFNγ) + log10(CXCL9) + log10(CXCL10)) in patients with rGBM (n = 15) evaluated relative to response. Left: box-and-whisker plot of CSF IFNγ pathway scores for PD versus SD or better following CAR-T treatment. The median and interquartile range with whiskers extending to the minimum and maximum values are depicted. Right: CSF IFNγ pathway scores plotted against time to progression in days, with the regression line for all arms depicted. Dose schedule (DS) indicated by dot size and P values determined by two-sided t-test.
