Fig. 8: Disabling FAS signaling enhances CAR-NK antitumor efficacy in vivo.
From: CAR-engineered lymphocyte persistence is governed by a FAS ligand–FAS autoregulatory circuit
a, Comparison of the in vitro cytolytic efficiencies of NK cells transduced with a WT or 1XX version of the 1928ζ CAR against Nalm6/mCherry at high versus low E:T ratios. Data are shown as mean ± s.e.m. using n = 3 biologically independent samples. Statistical comparisons were performed using a one-way ANOVA. NS, not significant (P > 0.05). b, Experimental design to compare the in vivo antitumor efficacy of human NK cells expressing the 1XX 1928ζ CAR ± a FAS-dominant negative receptor (ΔFAS) against established Nalm6 B-ALL at a high (top) versus low (bottom) E:T ratio. All mice received a twice-weekly i.p. injection of 1 μg of IL-15 pre-complexed with IL-15Rα-Fc (1:1 M). c, Survival curves for high (top) versus low (bottom) E:T ratios (PBS, n = 5; nontransduced NK cells, n = 5; tEGFR alone, n = 5; 1XX 1928ζ-tEGFR, n = 10; 1XX 1928ζ-ΔFAS-tEGFR, n = 10). Data are plotted as Kaplan–Meier curves with groups compared using a log-rank test. NS, not significant (P > 0.05). d, Model for the dichotomous functions of FAS-L on CAR-T and CAR-NK cellular persistence and antitumor efficacy. Cells colored in red indicate FAS-L-induced apoptosis.
