Figure 5.

ABL501 treatment exerts antitumor effects in mouse tumor models

(A–D) 1G4 T cells expressing an NY-ESO-specific TCR were adoptively transferred into NSG mice bearing A375-PD-L1 tumors. At 1 day following T cell transfer, the mice were intraperitoneally treated with hIgG4 (10 mg/kg), anti-LAG3 (10 mg/kg), anti-PD-L1 (10 mg/kg), or ABL501 (14 mg/kg, molar equivalent amount) on days 11, 13, 17, and 20 (five mice/group). Tumor samples were collected on day 21 and processed for single-cell suspensions and then subjected to FACS analysis. (A) Experimental scheme of an in vivo xenograft mouse tumor model (above). Mice were monitored for tumor growth, and means ± SEM of n = 5 mice/group are shown (below). (B) Summary plots showing the percentages (left panel) and numbers (right panel) of 1G4 TCR-CD8⁺ T cells in tumors per treatment group. (C) Representative FACS plot (left panel) and summary plot (right panel) show the percentages of IL-2, IFN-γ, or granzyme B by 1G4 TCR-CD8⁺ T cells in tumors per treatment group. (D) Heatmap plot shows the geometric MFI of the expression of the indicated cytokines by tumor infiltrating 1G4 TCR-CD8⁺ T cells. (E) CT26 cells with knockin human PD-L1 were subcutaneously injected into human LAG-3/PD-1 knockin BALB/c mice (n = 6–8/group). Mice were treated with the indicated concentrations of ABL501 three times at 7-day intervals. Tumor growth curves of individual mice (right panel) are shown. (F) MC38 cells with knockin human PD-L1 were subcutaneously injected into human LAG-3/PD-1/PD-L1 knockin C57BL/6 mice (n = 5/group). Mice were treated with ABL501 (10 mg/kg) or isotype control (8.5 mg/kg) four times at 3-day intervals. Tumor growth curves of individual mice (right panel) are shown. Significant differences between groups were determined by two-way ANOVA Tukey’s multiple comparison test. ∗p < 0.05, ∗∗p < 0.005, ∗∗∗p < 0.001, ∗∗∗∗p < 0.001, and ns.