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Antibody-dependent cellular cytotoxicity-null effector developed using mammalian and plant GlycoDelete platform
DC Field | Value | Language |
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dc.contributor.author | 김주영 | - |
dc.contributor.author | 정민규 | - |
dc.date.accessioned | 2023-03-03T02:58:54Z | - |
dc.date.available | 2023-03-03T02:58:54Z | - |
dc.date.issued | 2022-11 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/192947 | - |
dc.description.abstract | 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. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | Nature Publishing Group | - |
dc.relation.isPartOf | SCIENTIFIC REPORTS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Antibody-Dependent Cell Cytotoxicity | - |
dc.subject.MESH | Cricetinae | - |
dc.subject.MESH | Cricetulus | - |
dc.subject.MESH | Immune Checkpoint Inhibitors | - |
dc.subject.MESH | Immunoglobulin Fc Fragments* / metabolism | - |
dc.subject.MESH | Immunoglobulin G | - |
dc.subject.MESH | Nivolumab* | - |
dc.subject.MESH | Polysaccharides / metabolism | - |
dc.subject.MESH | Programmed Cell Death 1 Receptor | - |
dc.subject.MESH | Receptors, IgG / metabolism | - |
dc.title | Antibody-dependent cellular cytotoxicity-null effector developed using mammalian and plant GlycoDelete platform | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Pharmacology (약리학교실) | - |
dc.contributor.googleauthor | Cho Eun Kang | - |
dc.contributor.googleauthor | Seungeun Lee | - |
dc.contributor.googleauthor | Taeyoung Ahn | - |
dc.contributor.googleauthor | Dong Hye Seo | - |
dc.contributor.googleauthor | Byoung Joon Ko | - |
dc.contributor.googleauthor | Minkyu Jung | - |
dc.contributor.googleauthor | Jinu Lee | - |
dc.contributor.googleauthor | Joo Young Kim | - |
dc.contributor.googleauthor | Woo Taek Kim | - |
dc.identifier.doi | 10.1038/s41598-022-23311-9 | - |
dc.contributor.localId | A00942 | - |
dc.contributor.localId | A03606 | - |
dc.relation.journalcode | J02646 | - |
dc.identifier.eissn | 2045-2322 | - |
dc.identifier.pmid | 36347901 | - |
dc.contributor.alternativeName | Kim, Joo Young | - |
dc.contributor.affiliatedAuthor | 김주영 | - |
dc.contributor.affiliatedAuthor | 정민규 | - |
dc.citation.volume | 12 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 19030 | - |
dc.identifier.bibliographicCitation | SCIENTIFIC REPORTS, Vol.12(1) : 19030, 2022-11 | - |
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