Engineered Fc variant antibodies with enhanced ability to recruit complement and mediate effector functions.

ABSTRACT: Engineering the antibody Fc region to enhance the cytotoxic activity of therapeutic antibodies is currently an active area of investigation. The contribution of complement to the mechanism of action of some antibodies that target cancers and pathogens makes a compelling case for its optimization. Here we describe the generation of a series of Fc variants with enhanced ability to recruit complement. Variants enhanced the cytotoxic potency of an anti-CD20 antibody up to 23-fold against tumor cells in CDC assays, and demonstrated a correlated increase in C1q binding affinity. Complement-enhancing substitutions combined additively, and in one case synergistically, with substitutions previously engineered for improved binding to Fc gamma receptors. The engineered combinations provided a range o

SUBMITTER: Moore GL 

PROVIDER: S-EPMC2840237 | biostudies-literature | 2010 Mar-Apr

REPOSITORIES: biostudies-literature