FIGURE 7.

AL008 enhances the activity of T cell checkpoint blockade. (A) Transgenic mice that express human SIRPα and human CD47 (huSIRPα/huCD47) were generated and implanted with MC38 cells. Expression of huSIRPα on F4/80⁺ macrophages, Ly6C⁺ monocytes, and Ly6G⁺ neutrophils is shown in red. Expression of CD47 on F4/80⁺ macrophages is shown in blue. (B) MC38-huCD47⁺ cells were generated by deleting mouse CD47 from MC38 cells and expressing a huCD47 by lentivirus transduction. Expression of human and mouse CD47 on WT MC38 (gray) and MC38-huCD47⁺ (blue) cells is shown. (C) huSIRPA/huCD47 mice were implanted with MC38-huCD47 cells and received two doses of 3 mg/kg AL008, 10 mg/kg AL008, or isotype control. On days 1, 4, and 8 postdose, tumors were harvested and dissociated, and myeloid cells were stained for huSIRPα using an anti-SIRPα clone that does not compete with AL008 binding. The percentage of cell surface SIRPα is shown. (D) huSIRPα/huCD47 mice were implanted with MC38-huCD47⁺ cells and treated twice a week for 3 wk with 3 mg/kg anti–PD-L1 + 10 mg/kg mIgG2A, 10 mg/kg AL008 + 3 mg/kg anti–PD-L1, 10 mg/kg KWAR23 + 3 mg/kg anti–PD-L1, 10 mg/kg AL008, or with 3 mg/kg rat IgG2b + 10 mg/kg mIgG2A isotype control. Data are means ± SEM for 9–10 mice per group. The results were replicated, and data from two separate studies are shown. Unpaired Student t tests were performed. *p < 0.05, **p < 0.01.