Fc Engineering: Design, expression, and functional characterization of antibody variants with improved effector function

Abstract

Today monoclonal antibodies are widely used in cancer therapy. However, clinical experience as well as translational research into antibodies' pharmacology and effector mechanisms has identified limitations of antibody therapy, including inefficient effector cell recruitment or initiation of complement-dependent cytotoxicity (CDC). These insights opened alleys for further improvement of antibodies' immunomodulatory functions. While second generation antibodies were predominantly engineered to reduce immunogenicity, progress in antibody engineering now enables the generation of antibodies with novel interesting features. The introduction of Fc engineering technologies offers the potential to tailor Fc-mediated effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC), CDC or phagocytosis. Approaches to improve Fc-mediated effector mechanisms by Fc-engineering allow for the design of so-called fit-for-purpose antibodies or antibody-derivatives, hopefully overcoming some limitations of current forms of antibody therapy. © 2012 Springer Science+Business Media, LLC.