ISB 1342 induces potent killing of cell lines showing reduced sensitivity to daratumumab. (A) Absolute number of specific antibody bound per cell (sABC) indicating the relative CD38 density on MM cell lines. Data represent mean ± SD and were compared using a 1-way ANOVA followed by a Kruskall-Wallis post hoc comparison using KMS-12-BM as a reference. (B-D) Cytotoxicity of MM cell lines in the presence of daratumumab in CDC (B), ADCP (C), and ADCC (D) assays. Data represent mean ± SD of the maximum response from 4 donors in 2 independent experiments (B), from up to 10 donors in 3 independent experiments (C), and from 5 donors in 3 independent experiments (D), which were compared using a 1-way ANOVA followed by a Tukey post hoc comparison. (E) Cytotoxicity of MM cell lines in the presence of ISB 1342 and healthy PBMCs (E:T, 5:1) for 72 hours in a RDL assay. Data represent mean ± SD of EC₅₀ from 6 PBMC donors, compared using a 1-way ANOVA followed by Dunnett post hoc comparison to KMS-12-BM. (F-H) Schematic representation depicting the MMoAK assay, including 4 MoA: T-cell RDL, ADCC, ADCP, and CDC (F). Cytotoxicity of various MM cell lines in the presence of ISB 1342 or daratumumab, healthy PBMC (E:T, 5:1), normal human serum, and rhIL-2 for 48 hours in a MMoAK assay. Data represent mean ± SD of duplicates from 1 representative donor using nonlinear regression analysis (F), the mean ± SD of EC₅₀ from up to 10 PBMC donors per treatment, and the cell line from 6 independent experiments that were compared using a two-way ANOVA and Sidak post hoc test (G-H). ∗P < .05, ∗∗P < .01, ∗∗∗P < .0001, ∗∗∗∗P < .00001.