Figure 7.
disLCK-CAR-T cells have an enhanced therapeutic profile in vivo
(A) Schematic of the ex vivo analysis of CAR-T cells after administration in vivo.
(B) Bone marrow CAR-T cells were analyzed at day 11 or 18 after cancer cells injected, and percentage of memory T cells (CD45RO+) was detected by FACS. The left panel shows the representative FACS data, and the right panel shows the statistical summary. n = 4 mice per group, each dot = one mouse, CAR-T = blue square, disLCK-CAR-T = red round dot.
(C) Exhaustion marker expression on the CAR-T cells from bone marrow analyzed on day 10. The left panel shows the representative FACS data, and the right panel shows the statistical summary. n = 4 mice per group, each dot = one mouse, CAR-T = blue square, disLCK-CAR-T = red round dot. Cells with 3, 2, or 1 exhaustion marker expression (TIM-3, LAG-3, and PD-1) are designated as exhaustion (+), and cells without exhaustion marker expression are designated as exhaustion (−).
(D) Cell number of the CAR-T cells from bone marrow and spleen at days 10 and 16 after cancer cells were injected. 1.8 × 106 CAR-T cells were administered in each mouse at day 4 after 1.5 × 106 Nalm-6 cells were injected at day 0. n = 4 mice per group.
(E) Principal-component analysis (PCA) of conventional CAR-T and disLCK-CAR-T cell in vivo performance. Each dot = one mouse, disLCK-CAR-T = red round dots, conventional CAR-T = blue square dots.
(F) Heatmap of the in vivo performances of CAR-T cells after PCA. The columns are biological repeats. Each row represents PCA values of ex vivo data of each factor, memory is the CD45RO+ group, and exhaustion (−) and (+) are defined the same as in (C).
Data in (B)–(D) are means ± SD. Boxes in (B) (right panels) represent 95% confidence intervals. p values denoted as in the Figure 1 legend using Student’s t test.
See Figure S7F for additional data.