Neonatal Fc receptor (FcRn): a novel target for therapeutic antibodies and antibody engineering

The biomedical applications of antibodies as prophylactics, therapeutics and diagnostics are developing rapidly. Neonatal Fc receptor (FcRn) is a major IgG Fc receptor capable of facilitating the translocation of IgG. FcRn can protect IgG from intracellular catabolism, thereby increasing its half-life. In recent decade, the interaction between FcRn and the Fc region has been reported with the focuses on either prolonging the plasma half-life of therapeutic IgG or shortening the half-life of pathogenic IgG. The FcRn–IgG interaction can be altered by modifying the Fc region to change their affinity (increase or decrease), and/or by reducing the Fc fragments of IgG to enhance its penetration into tissues or cells. By over expression of FcRn, the exogenous catabolism can be reduced, meanwhile the circulating IgG level could be enhanced. It has been confirmed in different FcRn over-expressed transgenic mice models, substantial humoral responses against antigens with weak immunogenicity can be mounted. In addition, designing inhibitors for FcRn–IgG interaction is another application prospect for treating IgG-mediated autoimmune diseases. Recent research advancements strengthen the understanding that FcRn is a key and promising drugable target in IgG intervention in the field of antibody engineering.