Fig. 4: Modelling different leukaemia response scenarios post-CAR T cell therapy.
a, On-chip monitoring of tumour burdens in leukaemia chips of different response scenarios. Data were collected from three independent experiments (n = 3). Inset: the counts of CD19+ (blue lines) and CD19− (red lines) leukaemia blasts in the leukaemia bone marrow niche spiked with 5% CD19− leukaemia blasts (relapse scenario). b, Clinical data showing tumour burdens of patients with leukaemia during CAR T cell therapy. Data were pooled and adopted from Liu et al.50, where different clinical studies with 209 patients were collected and unified. Nonlinear fittings were applied to remission and relapse scenarios and linear regression was applied to resistance response with 95% confidence intervals. The coloured shadings in a and b indicate the 95% confidence intervals. c, Histogram showing the distance of CAR T cell to chip centre on days 2, 4 and 6. Representative data were from one of the three technical replicates with similar results (n = 3). d, Dynamic distribution of CAR T cell in remission, resistance and relapse scenarios on day 4, corresponding to c. Each dot represents a CAR T cell. Black dash circles indicated the three concentric regions, central sinus, medullary cavity and endosteum. Representative data were from one of the three technical replicates with similar results (n = 3). e, Surface expression of CD25 on CAR T cells from different response scenarios. Data were collected from three independent experiments (n = 3). One-way ANOVA followed by Tukey’s post hoc test, mean and s.e.m. f, ELISA measured secretions of IFNγ from leukaemia chips of different response scenarios. Data were collected from three independent experiments (n = 3). Two-way ANOVA followed by Tukey’s multiple comparisons test, mean and s.e.m. g, On-chip response curves of leukaemia chips built with different initial low or high leukaemia burdens. Data were collected from eight technical replicates (n = 8), mean and s.e.m. h,i, Surface expression of CD25 (h) and nuclear expression of Ki67 (i) on CAR T cells in different response scenarios in g. Data were collected from eight technical replicates (n = 8). One-way ANOVA followed by Tukey’s post hoc test, mean and s.e.m.
