Human CD45 BC8-PBD produced from SAv-drug conjugates targets human HSCs in vivo and prolongs survival in an AML xenograft model. (A) Schema for PDX AML model in NSGS mice and treatment with CD45-PBD. (B-C) Survival and peripheral blood tumor burden (human CD45⁺CD33⁺ cells) (B) and CBCs (C). Death or euthanasia of all individuals in a treatment group is indicated by “X.” One mouse in the CD45 BC8-PBD group that died at day +24 and showed no evidence of leukemia in the blood, spleen, or bone marrow is censored. (D) Schema for engraftment of cord blood–derived CD34⁺ HSCs in NSGS mice and depletion by CD45-PBD. (E) Frequencies of human CD45⁺ cells in the peripheral blood and absolute human CD34⁺ cell counts in the bone marrow of untreated and ADC-treated mice; for peripheral blood data, dotted lines represent individual mice and solid lines are means. One mouse death each in the no-ADC (day +19) and ISO-PBD (day +28) groups occurred before bone marrow CD34⁺ cell analysis. Numerical data are presented as mean ± SEM of mice from 2 (E) or 3 (B-C) independent experiments. Statistics: Mantel-Cox log-rank test (B), mixed-effects model for repeated measures (E, peripheral blood), 1-way ANOVA with Tukey correction for multiple comparisons (E, bone marrow). ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. ISO, isotype control; mIgG1, mouse immunoglobulin G1; ns, not significant; PDX, patient-derived xenograft; WBC, white blood cell count.