Combination of Dara and Hu5F9-IgG2σ in random de novo T-ALL PDX samples. (A) Antibody-dependent cellular phagocytosis in 12 random de novo T-ALL PDX samples treated with daratumumab (Dara), a CD47-blocking antibody (Hu5F9-IgG2σ), the combination (Dara + Hu5F9-IgG2σ [combi]), or no treatment (control) using live cell imaging. Error bars show standard error of the mean of technical triplicates. One representative experiment of 4 experiments with different donor macrophages is shown. The remaining experiments with other donor macrophages are depicted in supplemental Figure 3. (B) Summary of all ADCP in T-ALL PDX samples with human macrophages from 4 healthy donors. (C) In vivo phase 2–like preclinical study in an MRD-like setting with 6 random de novo T-ALL PDX samples injected into NSG mice and subjected to Dara, Hu5F9-IgG2σ, the combination (Dara + Hu5F9-IgG2σ [combi]), or no treatment (control). (D) In vivo phase 2–like preclinical study in an overt leukemia setting with 6 random de novo T-ALL PDX samples injected into NSG mice and subjected to Dara, Hu5F9-IgG2σ, the combination (Dara + Hu5F9-IgG2σ [combi]), or no treatment (control). The set of mice from patient #1 was excluded due to non-engraftment in this experiment. (E) Determination of blood and postmortem bone marrow (BM) blasts analyzed by using flow cytometry in mice injected with one random de novo T-ALL PDX sample and subjected to chemotherapy only (chemo only), the combination of Dara + chemo, Hu5F9-IgG2σ + chemo, both antibodies with chemo, or no treatment (control). Survival was analyzed by using the Kaplan-Meier method and log-rank statistics. Nonparametric Mann-Whitney U test (two-tailed). **P < .01, ***P < .001. ns, not significant; ROI, red object counts per image.