PF-06747143 reduces BM tumor burden in a dose-response dependent manner in a disseminated AML tumor model. MV4-11-Luc AML cells were implanted IV (1 × 106 cells) and allowed to spontaneously migrate and home in the BM for 11 days, when animals were randomized (n = 5-10 per group). (A) Treatment schematic representation. Animals were treated with IgG1 control or PF-06747143 Ab’s, subcutaneously, weekly, for 4 doses. Daunorubicin was dosed at 2 mg/kg, IV, 3 times (days 1, 3, and 5). Crenolanib was dosed at 7.5 mg/kg, IP, twice a day, on days 11 through 15 and days 25 through 29. (B) Tumor burden was determined by bioluminescence imaging and quantification. Data points represent the mean bioluminescence ± SEM. (C) Whole body bioluminescence representative imaging showing tumor burden in n = 5 mice per group over time. (D) On day 35, 3 days following the final Ab treatment, tumor burden was evaluated in PB and BM cells by flow cytometry, using hCD45 and hCD33 Ab’s as AML markers (n = 5-10 mice per group). Data points represent each individual mouse. (E) Kaplan-Meier survival curve (n = 5 animals per group), using hind leg paralysis as the end point.
