Fig. 5: Assessing functional performance of CAR T cell products.
a, On-chip leukaemia response curves under treatment of D3-CAR and D9-CAR T cells. Data were collected from three independent experiments (n = 3). b,c, Surface expression of CD25 (b) and nuclear expression of Ki67 (c) on D3-CAR and D9-CAR T cells after on-chip interaction with leukaemia blasts for 2 days with a dose of 10,000 CAR T cells. Data were collected from four technical replicates (n = 4). Unpaired, two-sided, Student’s t-test, mean and s.e.m. d, Comparison of T cell migration dynamics (left) and extravasation (right) of D3-CAR and D9-CAR within a 4 h monitoring period. Quantitative data were collected from three technical replicates (n = 3) with >100 T cells. Unpaired, two-sided, Student’s t-test, mean and s.e.m. e, Functional index of D3-CAR and D9-CAR. D3-CAR was normalized to D9-CAR, highlighting enhanced proliferation and cytokine secretion. a.u., absolute unit. Of note, the concentration of each cytokine was first normalized to that in the corresponding control group and averaged at equal weight to get the single number for cytokine secretion index. f, Comparative analysis of leukaemia burden on-chip treated with different patient-derived CAR T cell products (ProMab) with a dose of 10,000 CAR T cells. Data were collected from three technical replicates (n = 3) and normalized to day 0, mean and s.e.m. Data with statistical significance was determined by two-way ANOVA followed by Tukey’s post hoc test. g, Cytokine secretion index of different patient-derived CAR T cell products, benchmarked by an HD CAR T cell (dash line). PD145 CAR outperformed other PD CAR T cell products. h, On-chip response curves of leukaemia chips under treatment of different patient-derived CAR T cells with 2nd-gen (4-1BBζ-CAR19) or 4th-gen CAR (4-1BBζ-CAR19-IL18) designs with a dose of 625 CAR T cells. Data were collected from six technical replicates (n = 6). i, Cytokine secretion profiles of CAR19 and CAR19-IL18 on-chip (dose of 10,000 CAR T cells) on day 2 were examined by using a Human Inflammation Array C3 membrane kit with CAR T cell products of two patient donors (n = 2).
