Single-dose antitumor activity of SGN-CD33A in MDR-negative and MDR⁺ murine models of AML. Localized tumor models were developed in SCID mice with (A) MDR-negative HL-60 cells, (B) MDR⁺ HEL 92.1.7 cells, or (C-D) MDR⁺ TF1-α cells. Mice were dosed once with SGN-CD33A, nonbinding control ADC, GO, unconjugated h2H12ec, or SGD-1882 PBD dimer when tumors reached ∼100 mm³ (arrow). Antitumor activity was also assessed in disseminated models developed with (E) TF1-α and (F) cells from a patient with MDR⁺ relapsed AML disease. Seven days after intravenous administration of TF1-α cells, SCID mice were dosed once with SGN-CD33A, nonbinding control ADC or GO (arrow). Animals were monitored and euthanized on evidence of disease. For the primary AML model, NSG mice were injected with patient isolate, and when the tumor burden in the bone marrow approached 80%, as assessed by flow cytometry (left), mice were dosed on day 0 and day 11 with 300 μg/kg SGN-CD33A (right). AML blast percentages were determined in bone marrow aspirates from live mice (day 1 and day 10; n = 12/group) and in mice terminated on days 21 to 55 (n = 3/group). SGN-CD33A treatment had no adverse effects on the health of the mice at all of the doses tested.