XmAb5574-induced ADCC by NK cells against B-CLL cells is mediated through granzyme B and perforin–mediated pathways. NK cells (at 10⁶cells/mL) were treated with DMSO, granzyme B inhibitor DCI at 10μM (A), or a perforin inhibitor concanamycin A (CMA) at 50nM (B) for 30 minutes before incubation with allogeneic CLL cells. Ability of XmAb5574 to mediate ADCC against CLL cells through NK cells was diminished significantly in the presence of (A) DCI (17.4% decrease with DCI; 95% CI, 7.06-27.84; P = .007; n = 29, compared with DMSO*; at E/T of 25:1) but not with (B) CMA (9.15% decrease with CMA; 95% CI, 1.2% to −19.49%; P = .23; n = 29, compared with DMSO*; at E/T of 25:1) at the tested concentration. Error bars represent SEMs.