Establishment of FUT8 knockout Chinese hamster ovary cells: An ideal host cell line for producing completely defucosylated antibodies with enhanced antibody‐dependent cellular cytotoxicity
Abstract
To generate industrially applicable new host cell lines for antibody production with optimizing antibody‐dependent cellular cytotoxicity (ADCC) we disrupted both FUT8 alleles in a Chinese hamster ovary (CHO)/DG44 cell line by sequential homologous recombination. FUT8 encodes an α‐1,6‐fucosyltransferase that catalyzes the transfer of fucose from GDP‐fucose to N‐acetylglucosamine (GlcNAc) in an α‐1,6 linkage. FUT8−/− cell lines have morphology and growth kinetics similar to those of the parent, and produce completely defucosylated recombinant antibodies. FUT8−/−‐produced chimeric anti‐CD20 IgG1 shows the same level of antigen‐binding activity and complement‐dependent cytotoxicity (CDC) as the FUT8+/+‐produced, comparable antibody, Rituxan. In contrast, FUT8−/−‐produced anti‐CD20 IgG1 strongly binds to human Fcγ‐receptor IIIa (FcγRIIIa) and dramatically enhances ADCC to approximately 100‐fold that of Rituxan. Our results demonstrate that FUT8−/− cells are ideal host cell lines to stably produce completely defucosylated high‐ADCC antibodies with fixed quality and efficacy for therapeutic use. © 2004 Wiley Periodicals, Inc.
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The first FUT8 -/- cell line was created by sequential homologous recombination.
“The first FUT8 -/-cell line was created by sequential homologous recombination (Yamane-Ohnuki et al., 2004).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Yamane-Ohnuki et al., 2004
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- Authors
- Yamane‐Ohnuki, N., Kinoshita, S., Inoue‐Urakubo, M., Kusunoki, M., Iida, S., Nakano, R., Wakitani, M., Niwa, R., Sakurada, M., Uchida, K., Shitara, K., & Satoh, M.
- Affiliations
- Kyowa Kirin (Japan) (JP)
- Corresponding author
- Satoh, Mitsuo
- ORCID
- Uchida, Kazuhisa
- Venue
- Biotechnology and Bioengineering
- Publisher
- Wiley
- Published
- 2004-08-17
- Volume
- 87
- Issue
- 5
- Pages
- 614-622
- ISSN
- 0006-3592 (ISSN-L)
- 1097-0290
- OpenAlex
- W2115571948
- Cited by
- 572
- References
- 49
- Citations by year
- 2026: 16 · 2025: 22 · 2024: 27 · 2023: 18 · 2022: 20 · 2021: 31 · 2020: 28 · 2019: 30 · 2018: 40 · 2017: 36 · 2016: 24 · 2015: 29 · 2014: 29 · 2013: 21 · 2012: 32
- FWCI
- 6.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biotechnology and Bioengineering (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Keywords
- alpha-1,6-fucosyltransferase, antibody-dependent cellular cytotoxicity, CHO cells, FcγRIIIa, complement-dependent cytotoxicity, recombinant antibody production, homologous recombination, rituximab
- MeSH terms
- Alleles, Animals, Antibodies, Monoclonal, Antibody-Dependent Cell Cytotoxicity, Carbohydrate Sequence, Cricetulus, Enzyme-Linked Immunosorbent Assay, Fucosyltransferases, Genetic Vectors, Cricetinae, Humans, Immunoglobulin G, Oligosaccharides, Recombinant Fusion Proteins, Tumor Cells, Cultured, CHO Cells, Gene Transfer Techniques, Gene Targeting, Antigens, CD20
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