The SMAC mimetic birinapant synergizes with anti-CD3 to induce leukemic cell apoptosis. (A) Western blot analysis of IAP1 (top panel) and IAP2 (middle panel) expression in leukemic cells of UPNT760 T-ALL xenografted mice at 12 or 24 hours after administration of either 4 μg OKT3 (O, red writing) or OKT3/birinapant (20 mg/kg) (OB, purple writing). Control mice were treated with IgG2a/carrier solvent. Results from 2 independent mice are shown. Anti-hCD7 expression is used as loading control (lower panel). (B) NSG mice were injected with 106 UPNT760 T-ALL cells. At high leukemia burden, mice were treated with either control IgG2a/solvent (blue dots), IgG2a/birinapant (20 mg/kg, green triangles), 4 μg OKT3/solvent (red squares), or combination of OKT3 and birinapant (orange triangles) for 6 hours, after which time leukemia burden (hCD45/hCD7+ cells), annexin V/propidium iodide (PI) staining, and caspase 3/7 and caspase 8 activities were analyzed by flow cytometry. Ctl, control. ∗ P < 0.05; ∗∗∗ P < 0.001.
