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

DC Field Value Language
dc.contributor.author김주영-
dc.contributor.author정민규-
dc.date.accessioned2023-03-03T02:58:54Z-
dc.date.available2023-03-03T02:58:54Z-
dc.date.issued2022-11-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/192947-
dc.description.abstractCancer 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.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherNature Publishing Group-
dc.relation.isPartOfSCIENTIFIC REPORTS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAnimals-
dc.subject.MESHAntibody-Dependent Cell Cytotoxicity-
dc.subject.MESHCricetinae-
dc.subject.MESHCricetulus-
dc.subject.MESHImmune Checkpoint Inhibitors-
dc.subject.MESHImmunoglobulin Fc Fragments* / metabolism-
dc.subject.MESHImmunoglobulin G-
dc.subject.MESHNivolumab*-
dc.subject.MESHPolysaccharides / metabolism-
dc.subject.MESHProgrammed Cell Death 1 Receptor-
dc.subject.MESHReceptors, IgG / metabolism-
dc.titleAntibody-dependent cellular cytotoxicity-null effector developed using mammalian and plant GlycoDelete platform-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Pharmacology (약리학교실)-
dc.contributor.googleauthorCho Eun Kang-
dc.contributor.googleauthorSeungeun Lee-
dc.contributor.googleauthorTaeyoung Ahn-
dc.contributor.googleauthorDong Hye Seo-
dc.contributor.googleauthorByoung Joon Ko-
dc.contributor.googleauthorMinkyu Jung-
dc.contributor.googleauthorJinu Lee-
dc.contributor.googleauthorJoo Young Kim-
dc.contributor.googleauthorWoo Taek Kim-
dc.identifier.doi10.1038/s41598-022-23311-9-
dc.contributor.localIdA00942-
dc.contributor.localIdA03606-
dc.relation.journalcodeJ02646-
dc.identifier.eissn2045-2322-
dc.identifier.pmid36347901-
dc.contributor.alternativeNameKim, Joo Young-
dc.contributor.affiliatedAuthor김주영-
dc.contributor.affiliatedAuthor정민규-
dc.citation.volume12-
dc.citation.number1-
dc.citation.startPage19030-
dc.identifier.bibliographicCitationSCIENTIFIC REPORTS, Vol.12(1) : 19030, 2022-11-
Appears in Collections:
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

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