J6M0-mcMMAF broadly inhibits MM cell growth and survival without targeting BMSCs and effector cells. (A) Various MM cell lines (left panel) and patient MM cells (right panel) were cultured for 3 days, alone or with BMSCs, in the presence of J6M0-mcMMAF followed by luminescent viability assays. (B) Three MM cell lines were treated with serial dilutions of J6M0-mcMMAF or 10 μg/mL iso-mcMMAF (iso 10) overnight followed by caspase 3/7 activity assays. (C) NK cells were treated with J6M0-mcMMAF for 4 days, alone or with BMSCs. MM1Sluc cells, alone or with BMSCs, were included to show differential toxicity. (D) PBMCs, pretreated with or without lenalidomide (Len, 2μM), were treated for 3 days with J6M0-mcMMAF with or without BMSCs and in the presence or absence of OPM2 cells. (E) Monocytes (CD14⁺) were treated with J6M0-mcMMAF for 4 days, in the presence or absence of BMSCs or H929 MM cells.