(A) Romain and colleagues generated the CD33-specific Fc-engineered antibody DLE-HuM195 by introducing 3 amino acid exchanges (S239D-A330L-I332E) in the CH2 domain of HuM195. This Fc variant has been described by Lazar et al and results in enhanced Fc affinity to FcγRIIIa and reduced C1q binding activity. (B) The improved FcγRIIIa binding affinity of DLE-HuM195 resulted in stronger ADCC activity compared with the nonengineered counterpart. Using 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. The IgG model structure is based on a protein data bank file kindly provided by Mike Clark (http://www.path.cam.ac.uk/∼mrc7/).