Figure 7.
CD7KOCD7 CAR T cells control the progression of systemic T-ALL in the mouse xenograft model. (A) Schematic outline of the experiment. NSG mice (n = 5 per group) were injected intravenously with 1 × 106 GFP-FFluc CCRF cells followed by a single intravenous injection of 2 × 106 of control or CD7KO CD7 CAR T cells 3 days later. (B) Tumor burden was monitored weekly by measuring luminescence using IVIS imaging. (C) Overall kinetics of systemic tumor progression in mice. Each line denotes an individual animal. (D) Kaplan-Meier survival curve of mice injected with control or CD7KO CD7 CAR T cells. (E) Relative frequency of CAR T cells (hCD45+ GFP−) in peripheral blood of mice in stable remission (top) or during early stages of relapse (bottom) on day 34 after CAR T-cell injection. (F) Surface expression of CD7 on relapsed CCRF tumor cells in peripheral blood of 3 relapsed mice (CCRF m1-m3, blue histograms) in comparison with control in vitro propagated cells (red histogram). Open histogram denotes CD7-negative cell line Raji. Data represent 2 independent experiments. (G) CCRF GFP+ blasts were isolated from spleens of 3 relapsed mice and cocultured with CD7KO control or CD7 CAR T cells from 3 donors for 24 hours at a 1:1 E:T ratio. The numbers of viable tumor cells were counted at the end of coculture by flow cytometry using counting beads. *P < .05; **P < .01, by log-rank Mantel-Cox test; ****P < .0001.