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. 2016 Jul 25;126(8):3130–3144. doi: 10.1172/JCI83092

Figure 8. PD-1–blocking antibody restores the effector function of exhausted M28z CAR T cells in vitro and in vivo.

Figure 8

(A) M28z CAR T cells were stained with the PD-1–blocking antibody used for functional assays. For in vitro experiments (B–D), M28z CAR T cells were stimulated with MSLN+ tumor cells that had been treated with IFN-γ and TNF-α to upregulate PD-1 ligands. M28z CAR T cells treated with PD-1–blocking antibody (10 μg/ml) demonstrated a small enhancement in accumulation (B), an increase in cytolytic function upon the third stimulation (C), and enhanced effector cytokine secretion (D). Student’s t tests were performed for statistical significance. Data represent the mean ± SEM of triplicates and are representative of 2–3 independent experiments. (E) Injection of PD-1–blocking antibody rescues M28z CAR T cells in vivo as shown by tumor BLI in a model treating established high tumor burdens with a single low dose of intrapleurally administered M28z CAR T cells. PD-1–blocking antibody (10 mg/kg) was injected intraperitoneally 3 times on days 30, 35, and 40 or continuously injected every 5 days from day 0 to day 85 following T cell injection. n = 6–9 mice per group. *P < 0.05.