Yoo Jin Oh

Production of therapeutic monoclonal antibody (mAb) in transgenic plants has several advantages such as large‐scale production and the absence of pathogenic animal contaminants. However, mAb with high mannose (HM) type glycans has shown a faster clearance compared to antibodies produced in animal cells. The neonatal Fc receptor (FcRn) regulates the persistence of immunoglobulin G (IgG) by the FcRn‐mediated recycling pathway, which salvages IgG from lysosomal degradation within cells. In this study, Fc‐engineering of antirabies virus therapeutic mAb SO57 with the endoplasmic reticulum (ER)‐retention peptide signal (Lys‐Asp‐Glu‐Leu; KDEL) (mAb p K SO57) in plant cell was conducted to enhance its binding activity to human neonatal Fc receptor (hFcRn), consequently improve its serum half‐life. Enzyme‐linked immunosorbent assay (ELISA) and Surface plasmon resonance assay showed altered binding affinity of the Fc region of three different mAb p K SO57 variants [M252Y/S254T/T256E (MST), M428L/N434S (MN), H433K/N434F (HN)] to hFcRn compared to wild type (WT) of mAb p K SO57. Molecular modeling data visualized the structural alterations in these mAb p K SO57. All of the mAb p K SO57 variants had HM type glycan structures similar to the WT mAb p K SO57. In addition, the neutralizing activity of the three variants against the rabies virus CVS‐11 was effective as the WT mAb p K SO57. These results indicate that the binding affinity of mAb p K SO57 variants to hFcRn can be modified without alteration of N‐ glycan structure and neutralization activity. Taken together, this study suggests that Fc‐engineering of antirabies virus mAb can be applied to enhance the efficacy of therapeutic mAbs in plant expression systems.