Fc-optimized antibodies quickly pull the trigger.

In this issue of Blood, Romain et al demonstrate that natural killer (NK) cell–mediated killing of tumor cells coated with the Fc-optimized CD33 antibody DLE-HuM195 reveals a distinct kinetic profile. The presented work gives important novel insights into the mechanism of effector cell–mediated target cell killing triggered by Fc-engineered antibodies and explains how they achieve a higher antibody-dependent cell-mediated cytotoxicity (ADCC) potency than native immunoglobulin G1 (IgG1) antibodies. Using time-lapse imaging microscopy in nanowell grids (TIMING), the authors were able to demonstrate at the single-cell level that antibody Fc engineering improves frequency and promotes kinetic boosting of serial killing mediated by NK cells.