In vivo VpreB1-ADC efficacy against a TCF3::PBX1 B-ALL PDX model. NSG mice were transplanted through tail vein injection with 1 × 106 PDX B5 model cells. When 1% to 5% leukemia cells were detectable in the peripheral blood, mice were treated with VpreB1-ADC 2 mg/kg or PBS control (n = 9 mice per group) IP on days 1, 4, and 7. (A-C) After 48 hours from completing the therapy, mice from each group were euthanized, femurs and spleens isolated, and leukemia burden assessed using either flow cytometry (human CD19 and CD45 antibodies) or IHC (human CD19). Representative flow cytometry plots (A) with quantification (B) and IHC (C) images are illustrated. Several mice died due to rapid leukemia progression before randomization and therapy initiation, and, as a result, only 1 (PBS) and 2 (VpreB1-ADC) mice were available for flow cytometry and IHC. (D) The remaining 6 mice were monitored for survival and Kaplan-Meier curves generated. The gray square indicates treatment duration. The log-rank (Mantel-Cox) test was used to compare the survival curves; ∗∗P < .01. (E) On day +168 of treatment, the 6 remaining mice from the VpreB1-ADC group were euthanized, bone marrow stained with human CD19 and CD45 antibodies, and assessed by flow cytometry (supplemental Figure 7 reveals the flow cytometry plots and gating strategy). H&E, hematoxylin and eosin.
