Fig. 1. ATR inhibition has immune driven CD8⁺ T-cell dependent antitumor activity in syngeneic immunocompetent mouse tumor models.

a Tumor growth rate (TGR) for CT26 (N = 10), MC38 (N = 20 for vehicle and PD-1 groups and 23 for two other groups), 4T1 (N = 12), and A20 (N = 15 for vehicle group and N = 10 for all other groups). TB mice treated as indicated. Ceralasertib (25 mg/kg p.o. b.i.d.), PD-L1 antibody (αPD-L1; 10 mg/kg i.p. b.i.w) b Kaplan–Meier survival (time-to-event) plot for mice bearing CT26 tumors. An event was scored when a tumor volume exceeded 1 cm³. Log-rank (Mantel–Cox) test was used. c TGR for CT26 tumors in mice treated with ceralasertib with or without CD8 T-cell depleting antibody (αCD8). (N = 10). d Tumor growth in athymic MC38 TB mice treated as in (a). (N = 10). e Immunohistochemistry (IHC) analysis of proportion of CD8⁺ T-cells in CT26 tumors from mice treated with vehicle (N = 9) or ceralasertib (N = 10) following 7 days-on (on day 8), intermittent 7 days-on/7 days-off (on day 15) (vehicle N = 8, cerala N = 12) or continuously on-treatment for 15 days (N = 12). Top panel: cumulative results with bar charts showing individual tumors, mean and SEM. Bottom panel: representative images also shown with CD8⁺ T-cells stained brown. Scale bar = 50 µm. f Combined tumor growth rate analysis in 3 independent experiments comparing intermittent 7 days-on/7 days-off versus continuous ceralasertib dosing in CT26 TB mice. The number of mice per group are shown on the plot. Tumor response classification was obtained using INSPECTumors (see methods). Non-significant differences (p > 0.05) are denoted as NS or by the absence of p values (to maintain readability of the figures). In all graphs except b, one-way ANOVA with correction for multiple comparisons was used for statistical analysis. In all graphs box-whisker plots shows individual tumors, group median and min-max values. Source data are provided as a Source Data file.