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The B cell death function of obinutuzumab-HDEL produced in plant (Nicotiana benthamiana L.) is equivalent to obinutuzumab produced in CHO cells

Authors
 Jin Won Lee  ;  Woon Heo  ;  Jinu Lee  ;  Narae Jin  ;  Sei Mee Yoon  ;  Ki Youl Park  ;  Eun Yu Kim  ;  Woo Taek Kim  ;  Joo Young Kim 
Citation
 PLoS One, Vol.13(1) : e0191075, 2018 
Journal Title
 PLoS One 
Issue Date
2018
MeSH
Animals ; Monoclonal Antibodies, Humanized/*pharmacology ; Immunological/*pharmacology Antineoplastic Agents ; B-Lymphocytes/*cytology ; CHO Cells ; *Cell Death ; Cricetinae ; Cricetulus ; Epitopes/immunology ; Flow Cytometry ; Plant Leaves/metabolism ; Tobacco/*genetics
Abstract
Plants have attracted attention as bio-drug production platforms because of their economical and safety benefits. The preliminary efficacy of ZMapp, a cocktail of antibodies produced in N. benthamiana (Nicotiana benthamiana L.), suggested plants may serve as a platform for antibody production. However, because the amino acid sequences of the Fab fragment are diverse and differences in post-transcriptional processes between animals and plants remain to be elucidated, it is necessary to confirm functional equivalence of plant-produced antibodies to the original antibody. In this study, Obinutuzumab, a third generation anti-CD20 antibody, was produced in N. benthamiana leaves (plant-obinutuzumab) and compared to the original antibody produced in glyco-engineered Chinese hamster ovary (CHO) cells (CHO-obinutuzumab). Two forms (with or without an HDEL tag) were generated and antibody yields were compared. The HDEL-tagged form was more highly expressed than the non-HDEL-tagged form which was cleaved in the N-terminus. To determine the equivalence in functions of the Fab region between the two forms, we compared the CD20 binding affinities and direct binding induced cell death of a CD20-positive B cells. Both forms showed similar CD20 binding affinities and direct cell death of B cell. The results suggested that plant-obinutuzumab was equivalent to CHO-obinutuzumab in CD20 binding, cell aggregation, and direct cell death via binding. Therefore, our findings suggest that Obinutuzumab is a promising biosimilar candidate that can be produced efficiently in plants.
Files in This Item:
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DOI
10.1371/journal.pone.0191075
Appears in Collections:
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
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/162102
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