FcγR:: The key to optimize therapeutic antibodies?

The binding of IgG to receptors for the Fc region of IgG (Fc gamma R) is a critical step for the initiation and the control of effector immune functions. Activating Fc gamma R induce antibody-dependent cell cytotoxicity (ADCC), endocytosis of immune complexes followed by antigen presentation, phagocytosis, and release of cytokines or pro-inflammatory mediators. By contrast, inhibitory Fc gamma R regulate immune responses by inhibiting the activation of B lymphocytes, monocytes, mast cells and basophils, induced through activating receptors. Studies with Fc gamma R-deficient mice support the critical role of the different Fc gamma R in the in vivo functional effects of therapeutic monoclonal antibodies. Structural studies have provided detailed insights in the molecular mechanisms that govern IgG/Fc gamma R interactions. The importance of the sugar components linked to asparagine 297 in the function of IgG has been also highlighted. These data have led to the engineering of a new generation of monoclonal antibodies for therapeutic use with optimized effector functions. (c) 2007 Elsevier Ireland Ltd. All rights reserved.