FcgammaR: The key to optimize therapeutic antibodies?
The binding of IgG to receptors for the Fc region of IgG (FcgammaR) is a critical step for the initiation and the control of effector immune functions. Activating FcgammaR 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 FcgammaR regulate immune responses by inhibiting the activation of B lymphocytes, monocytes, mast cells and basophils, induced through activating receptors. Studies with FcgammaR-deficient mice support the critical role of the different FcgammaR in the in vivo functional effects of therapeutic monoclonal antibodies. Structural studies have provided detailed insights in the molecular mechanisms that govern IgG/FcgammaR 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.
Sibéril
Sophie
S
Unité INSERM 255, IFR58, Université René Descartes-Paris 5, Université Pierre et Marie Curie-Paris 6, Centre de Recherches Biomédicales des Cordeliers, Paris, France.
Dutertre
Charles-Antoine
CA
Fridman
Wolf-Herman
WH
Teillaud
Jean-Luc
JL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D000918:Antibody Specificity; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends*; D006801:Humans; D017452:Receptors, IgG / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D017452:Receptors, IgG