Efficacy of PF-06747143 and role of Fc-effector function in the Ramos NHL efficacy model. Ramos cells were implanted subcutaneously (5 × 106 cells), and when mean tumor volume reached 350 to 400 mm3, mice were randomized (n = 10-12 per group). Arrows indicate Ab treatment days. Data points represent the mean tumor volume ± SEM. (A) Animals were treated weekly, subcutaneously, with Ab’s at 10 mg/kg for 2 doses, on days 1 and 8. (B) Animals were treated weekly, subcutaneously, with control IgG1 Ab at 10 mg/kg and PF-06747143 at 0.1, 1, 10, and 30 mg/kg for 4 doses, or until day 21. (C) Animals were treated weekly, subcutaneously, with m15-IgG1 or m15-IgG4 Ab’s at 1 and 10 mg/kg for 3 doses. Study was terminated at day 15. (D) Antibody exposure was evaluated 24 hours after last dose. Serum from 3 animals per group was collected, and human IgG concentration determined by enzyme-linked immunosorbent assay. Bars points represent the mean concentration ± SEM. (E) Cleaved caspase-3 in tumor tissue collected 48 and 72 hours post–Ab treatment at 10 mg/kg was determined by western blot (n = 3 animals per group).
