XmAb5592 induces strong MM cell lysis by degranulation of NK cells even in the presence of BMSCs. (A) XmAb5592-mediated lysis against MM1S, MM1R, and INA-6 MM cells was measured by calcein-AM release ADCC assay, in the presence or absence of BMSCs. Data were obtained in triplicate and represent the mean ± SD. (B) MM1S target cells and NK effector cells were incubated with serial dilutions of antibodies in the presence and absence of BMSCs, followed by dual-color flow cytometry analysis to determine the percentage of CD107a⁺ NK cells. Data were obtained in triplicate and represent the mean ± SD. XmAb5592 induced ∼ 10-fold more NK degranulation than the IgG1 analog in a dose dependent manner, regardless of the presence of BMSCs. (C) Calcein-AM release based ADCC assay was simultaneously performed (as in panel B) for XmAb5592 and the IgG1 analog treatment groups, in the presence or absence of BMSCs.