Fc engineered anti-virus therapeutic human IgG 1 expressed in plants with altered binding to the neonatal Fc receptor.

Autor: Park SA; Department of Medicine, BioSystems Design Lab, College of Medicine, Chung-Ang University, Dongjak-gu, Seoul, Republic of Korea., Lee Y; College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea., Hwang H; Department of Medicine, BioSystems Design Lab, College of Medicine, Chung-Ang University, Dongjak-gu, Seoul, Republic of Korea., Lee JH; Department of Medicine, BioSystems Design Lab, College of Medicine, Chung-Ang University, Dongjak-gu, Seoul, Republic of Korea., Kang YJ; Department of Medicine, BioSystems Design Lab, College of Medicine, Chung-Ang University, Dongjak-gu, Seoul, Republic of Korea., Kim Y; Department of Medicine, BioSystems Design Lab, College of Medicine, Chung-Ang University, Dongjak-gu, Seoul, Republic of Korea., Jin C; Department of Medicine, BioSystems Design Lab, College of Medicine, Chung-Ang University, Dongjak-gu, Seoul, Republic of Korea., An HJ; Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, Republic of Korea., Oh YJ; Department of Applied Experimental Biophysics, Johannes Kepler University Linz, Linz, Austria., Hinterdorfer P; Department of Applied Experimental Biophysics, Johannes Kepler University Linz, Linz, Austria., Kim E; Global AI Drug Discovery Center, College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea., Choi S; Global AI Drug Discovery Center, College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea., Ko K; Department of Medicine, BioSystems Design Lab, College of Medicine, Chung-Ang University, Dongjak-gu, Seoul, Republic of Korea.
Jazyk: angličtina
Zdroj: Biotechnology journal [Biotechnol J] 2024 Mar; Vol. 19 (3), pp. e2300552.
DOI: 10.1002/biot.202300552
Abstrakt: 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.
(© 2024 Wiley‐VCH GmbH.)
Databáze: MEDLINE
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