Figure 2.
SAR442085 shows enhanced antitumor ADCC and ADCP activity in vitro as compared with daratumumab and isatuximab. (A-F) The ADCC activity of NK-92 cells expressing FcγRIIIa-158F or FcγRIIIa-158V against RPMI-8226 (A-B), MOLP8 cells (C-D), or KMS-12-BM cells (E-F) was analyzed in the presence of increasing concentrations of Ig control, SAR442085, daratumumab, or isatuximab by calcein release assay after 1 hour at an effector to target ratio of 5:1. (G-H) The tumor cell lysis of CTV-labeled RPMI-8226 (G) or KMS-12-BM (H) cell lines incubated with increasing concentrations of Ig control, SAR442085, daratumumab, or isatuximab was evaluated by flow cytometry in the presence of healthy donor PBMCs after 18 hours at an effector to target ratio of 50:1. (I) The ADCC activity against CTV-labeled RPMI-8226 by healthy donor NK cells (HD NK) was measured by calcein release in the presence of the indicated mAbs (effector/tumor ratio = 10:1). (J) The phagocytosis was evaluated by flow cytometry using PKH26-labeled macrophages and PKH67-labeled RPMI8826 cells. All graphs represent the mean ± standard error of the mean (SEM) of pooled dose-response curves. Relative EC50 values (geometric mean) and maximum killing values (mean) for each dose-response curve were calculated. Statistical differences between groups were determined by a ratio paired t test for relative EC50 and by a paired Student t-test for maximum killing values. *P < .05; **P < .01, ***P < .001.