ISB1342 induces the killing of MM cell lines in vitro via T-cell engagement. (A) Representative confocal image of ISB 1342 (white) at the synapse between T cell (green) and KMS-12-BM MM cell line (blue) acquired with Zeiss LSM 800 inverted confocal microscope, magnification ×40. (B-F) Cytotoxicity of KMS-12-BM MM cell line (B) and T-cell activation (C), proliferation (D), and degranulation (E) after treatment with ISB 1342 or control molecules in the presence (F) or absence (B-E) of soluble CD38 (sCD38) and healthy PBMC (E:T, 5:1) for 72 hours. Data represent the mean ± SD from 3 PBMC donors performed in 2 independent experiments (B-E) or mean ± SD of EC₅₀ from 3 donors that were compared with the condition without sCD38 using a 1-way ANOVA followed by a Dunnett post hoc comparison (F). (G-H) Cytotoxicity of the RPMI8226 MM cell line (G) and cytokine release (H) in the presence of ISB 1342 ± dexamethasone and healthy PBMC (E:T, 10:1) for 48 hours. Data represent mean ± SD of EC₅₀ compared using a paired t test (G) and mean ± SD at the maximum dose of ISB 1342 tested compared using a paired t test (H) from 6 PBMC donors and performed in 2 independent experiments. ∗∗P < .01, ∗∗∗P < .001. ns, not significant. ANOVA, analysis of variance.