In vitro antibody-dependent cell-mediated cytotoxicity (ADCC) activity. (a-e) ADCC with JIMT-1 as target cells and purified natural killer (NK) cells from two or three independent donors for each CD16A genotype (F/F, F/V, or V/V) as effectors using a 3:1 effector/target ratio. (f-m) ADCC with breast and non-breast cancer cell lines expressing HER2 at different levels as target cells and peripheral blood mononuclear cells from three to six independent CD16A-158F carriers as effectors using a 30:1 effector/target ratio. Fold increases in percentage maximal lysis by MGAH22 relative to RES120 and EC50 values are plotted according to CD16A genotype of effectors (d, e) or number of HER2-binding sites per target cell (l, m). Data are presented as mean ± standard error of the mean. EC50, effective concentration for 50% lysis; MGAH22, chimeric anti-HER2 monoclonal antibody with an optimized Fc domain; RES120, chimeric anti-HER2 monoclonal antibody with wild-type human immunoglobulin G 1 Fc domain.