Extended Data Fig. 8: In vivo CAR-T cell expansion is CD8 predominant and relates to exhaustion phenotype of CAR-T products.
a,b Peak CD19-22.BBZ cells as measured by flow cytometry compared by (a) disease type and (b) dose level. No significant difference observed. c,d. CD19-22.BB.z AUC was measured by the trapezoidal method from infusion until Day 60 post infusion.Grades 2-4 (d) CRS (p = 0.04) and (c) neurotoxicity (p = 0.03) associated with higher CD19-22.BBZ AUC. Comparisons by Wilcoxon rank sum. e, Area under the curve calculated by trapezoidal integration of CD4 and CD8 CD19-22.BB.z cells from infusion to 2 months post infusion. The AUC for CD8 was greater than that of CD4 (p = 1.2 × 10−5) f, Peak expansion of CD4 and CD8 CD19-22.BB.z-CAR T cells measured by flow cytometry. Peak CD8 CD19-22.BB.z-CAR was greater than that of CD4 (p = 6.0 × 10−6). Comparison in e and f performed by paired Wilcoxon signed rank test. g, Change in the CD4:CD8 ratio from CD19-22.BB.z infusion product to peak expansion, shows the outgrowth of CD4 cells during manufacturing is not seen in the patients at time of peak CAR expansion, where CD8 CAR T+ cells are more abundant. N = 38 patients for a-g. h,i Significantly higher percentage of CD4 CAR T cells in the infusion product express CD39 (p = 5.2 × 10−8) and PD-1 (p = 1.2 × 10−10) compared to CD8 CAR-T cells (Wilcoxon signed rank) (n = 34 patients). Gating on CD3+ CAR+ cells. Box plot center line corresponds to the median; hinges correspond to the 25th and 75th percentiles with the whiskers extending to the smallest or largest value at most 1.5 x IQR from the hinge. All tests were two-sided and not adjusted for multiple comparisons.
