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Antibody-dependent cellular cytotoxicity-null effector developed using mammalian and plant GlycoDelete platform

 Cho Eun Kang  ;  Seungeun Lee  ;  Taeyoung Ahn  ;  Dong Hye Seo  ;  Byoung Joon Ko  ;  Minkyu Jung  ;  Jinu Lee  ;  Joo Young Kim  ;  Woo Taek Kim 
 SCIENTIFIC REPORTS, Vol.12(1) : 19030, 2022-11 
Journal Title
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Animals ; Antibody-Dependent Cell Cytotoxicity ; Cricetinae ; Cricetulus ; Immune Checkpoint Inhibitors ; Immunoglobulin Fc Fragments* / metabolism ; Immunoglobulin G ; Nivolumab* ; Polysaccharides / metabolism ; Programmed Cell Death 1 Receptor ; Receptors, IgG / metabolism
Cancer therapy using immune checkpoint inhibitor antibodies has markedly shifted the paradigm of cancer treatment. However, methods completely eliminating the effector function of these signal-regulating antibodies is urgently required. The heterogeneity of glycan chains in antibodies limits their use as therapeutic agents due to their variability; thus, the development of uniform glycan chains is necessary. Here, we subjected the anti-programmed cell death protein (PD)-1 antibody nivolumab, a representative immune checkpoint inhibitor, to GlycoDelete (GD) engineering to remove the antibody-dependent cellular cytotoxicity (ADCC) of the antibody, leaving only one glycan in the Fc. Glyco-engineered CHO cells were prepared by overexpressing endo-β-N-acetyl-glucosaminidase (Endo T) in CHO cells, in which N-acetyl-glucosaminyl-transferase I was knocked out using Cas9. GD IgG1 nivolumab and GD IgG4 nivolumab were produced using GD CHO cells, and glycan removal was confirmed using mass spectrometry. Target binding and PD-1 inhibition was not altered; however, ADCC decreased. Furthermore, the IgG4 form, determined to be the most suitable form of GD nivolumab, was produced in a plant GD system. The plant GD nivolumab also reduced ADCC without affecting PD-1 inhibitory function. Thus, CHO and plant GD platforms can be used to improve signal-regulating antibodies by reducing their effector function.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Joo Young(김주영) ORCID logo https://orcid.org/0000-0003-2623-1491
Jung, Min Kyu(정민규) ORCID logo https://orcid.org/0000-0001-8281-3387
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