Figure 6.
ISB 1342 controlled tumor growth in vivo in the KMS-12-BM xenograft hPBMC-transferred NSG mouse model. (A-B) Experimental design (A) and measurement of tumor growth (B) in the KMS-12-BM subcutaneously xenograft hPBMC-transferred NSG mouse model. In vivo activity was followed for ISB 1342 at 0.5 mg/kg injected IV once per week and daratumumab at 16 mg/kg injected IV twice per week, both for 3 weeks with 8 mice per group. Data are mean (mm3) ± SD determined by caliper measurements. Data were compared for both models using 2-way ANOVA followed by Tukey post hoc comparison. ∗Significant differences between ISB 1342 and vehicle control; # shows differences between daratumumab and ISB 1342. (C-D) Infiltration of hCD45+ cells (defined as live hCD45+mCD45–) (C) and T cells (hTCRαβ+CD14–CD19–CD56–CD45+) (D) in tumors of KMS-12-BM xenografted mice after vehicle, ISB1342 or daratumumab treatments. Data are mean ± SD for 5 mice compared using 1-way ANOVA followed by Dunnett post hoc test to ISB 1342. (E) Representative dot plots showing activation profile (CD25 and CD69 expression) on tumor-infiltrating T-cell activation in vehicle, daratumumab, and ISB 1342-treated mice. (F) CD38 expression on MM cells in tumors (KMS-12-BM model). Data are mean ± SD compared using 1-way ANOVA followed by Tukey post hoc test; ∗P ≤ .05.