XmAb5574 functionally activates NK cells. (A) XmAb5574-mediated NK-cell activation was determined by characterization of surface expression of CD107a by FACS analysis on freshly isolated NK cells after 4-hour stimulation by 20 μg/mL of respective antibody coated on a 96-well flat-bottom plate. XmAb5574 was significantly more effective in up-regulation of surface expression of CD107a than was XmAb5603 (19.4% higher; 95% CI, 9.6%-29.2%; *P = .005), trastuzumab (17.6% higher; 95% CI, 7.8%-27.4%; P = .006), or rituximab (12.8% higher; 95% CI, 0.2%-25.3%; P = .04; n = 5). (B) Representative FACS density plots showing expression of CD107a in CD56⁺ NK cells. Individual percentages of double-positive cells are shown in inserts. (C) NK-cell stimulation by fixed XmAb5574 resulted in a higher production of IFN-γ in cell-free culture supernatant that was harvested after 4 hours and analyzed for levels of IFN-γ by an enzyme-linked immunosorbent assay, compared with XmAb5603 (6.4 times higher; 95% CI, 2.13-19.19; *P = .007) or trastuzumab (4.68 times higher; 95% CI, 0.24-2.20; P = .008) or rituximab (5.95 times higher; 95% CI, 2.3-15.41; P = .004; n = 4). Error bars represent SEMs.