Figure 2.
CD45.2-PNU and CD45.2-PBD deplete B6 HSCs in vivo, with greater nonspecific toxicities for the PNU payload. B6 mice were either untreated (no ADC) or infused with 60 μg ADC produced by combining the indicated biotinylated antibodies with SAv-drug conjugates (on day −7). Mice were then euthanized and analyzed 7 days later (day 0). (A) Weight change on day 0 compared with immediately before ADC treatment on day −7. (B) Total cellularity of the spleen and bone marrow. (C) Counts of CD48−CD150+ Lin–Sca1+c-Kit+ cells in the bone marrow (SLAM-LSK population; HSC), and total CFUs from the bone marrow of ADC-treated mice assessed after an 8-day incubation in complete mouse methylcellulose. (D) CBCs; dotted lines indicate the lower reference limit for each assay. For all panels, each data point represents a single mouse, and bars represent mean ± SEM from mice accumulated over 3 independent experiments. Statistics: 1-way analysis of variance (ANOVA) with Dunnett’s correction for multiple comparisons (normally distributed data sets) or Kruskal-Wallis test with Dunn’s correction for multiple comparisons (nonnormally distributed data sets). ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. ns, not significant; WBC, white blood cell count.

CD45.2-PNU and CD45.2-PBD deplete B6 HSCs in vivo, with greater nonspecific toxicities for the PNU payload. B6 mice were either untreated (no ADC) or infused with 60 μg ADC produced by combining the indicated biotinylated antibodies with SAv-drug conjugates (on day −7). Mice were then euthanized and analyzed 7 days later (day 0). (A) Weight change on day 0 compared with immediately before ADC treatment on day −7. (B) Total cellularity of the spleen and bone marrow. (C) Counts of CD48−CD150+ Lin–Sca1+c-Kit+ cells in the bone marrow (SLAM-LSK population; HSC), and total CFUs from the bone marrow of ADC-treated mice assessed after an 8-day incubation in complete mouse methylcellulose. (D) CBCs; dotted lines indicate the lower reference limit for each assay. For all panels, each data point represents a single mouse, and bars represent mean ± SEM from mice accumulated over 3 independent experiments. Statistics: 1-way analysis of variance (ANOVA) with Dunnett’s correction for multiple comparisons (normally distributed data sets) or Kruskal-Wallis test with Dunn’s correction for multiple comparisons (nonnormally distributed data sets). ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. ns, not significant; WBC, white blood cell count.

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