Figure 4.

Antileukemic activity of CD70-CAR T cells in 2 murine AML xenograft models and against primary AML blast cells. (A) The experimental setup of the Molm-13 xenograft model. CD70-CAR T cells (5 × 10⁶) were injected 4 days after engraftment of luciferase-labeled Molm-13 cells (1 × 10⁶). BLI was performed before T-cell injection on day 0 and weekly thereafter (n = 5 for each treatment group). (B) BLI on the indicated days (after T-cell injection) of mice with Molm-13 cell engraftment and treatment with CD70-CAR or NT T cells. (C) Quantitative analysis of bioluminescence signals for individual mice from each treatment group. (D) Kaplan-Meier survival plot of mice treated with CD70-CAR or NT T cells. The log-rank (Mantel-Cox) test was used to perform statistical analyses of survival between the treatment groups. (E) The experimental setup of the THP-1 xenograft model. After sublethal irradiation, NSG mice underwent injection of 1 × 10⁶ luciferase-labeled THP-1 tumor cells. 4 days later, after engraftment, the mice then received an injection of 5 × 10⁶ CD70-CAR or NT T cells and were subsequently monitored by BLI. (F) Quantitative analysis of bioluminescence signals for individual mice with THP-1 tumor cell engraftment and treatment with LF-28z-, CD27z-CAR, or NT T cells. (G) Cytotoxicity of LF-28z- and CD27z-CAR T cells Ts against AML blasts from 3 patients with AML and various levels of CD70 expression was determined with a chromium-51 release assay. Data are the mean percentage of lysis ± standard deviation at an E:T target ratio of 40:1 from 3 different donors, with 3 technical replicates. *P < .05; **P < .01; ***P < .001, by unpaired Student t test.