Figure 6.

PF-06747143 reduces BM tumor burden in a PDX chemoresistant AML tumor model. (A) NSG mice received 150 cGy whole body irradiation, and within 24 hours, 1.5 × 10⁶ PDX BM cells were implanted IV and allowed to spontaneously migrate and home in the BM for 43 days, when tumor burden in PB reached 0.8% to 1.6%. Animals were then randomized in 5 animals per treatment group and treated with IgG1 control or PF-06747143 Ab’s, subcutaneously, weekly, for 8 doses. Daunorubicin was dosed at 1.5 mg/kg, IV, 3 times per week, for 2 cycles. Ara-C was dosed at 15 mg/kg, IP, once per day, from days 43 through 50 and days 64 through 71. On day 99, n = 5 animals per group were euthanized, and PB and BM samples were analyzed by flow cytometry to detect CXCR4⁺ malignant AML cells (hCD45⁺ and hCD33⁺) (B) or total AML cells (hCD45⁺ and hCD33⁺) (C).