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.com
Volume 9, Issue 5 (Suppl)
J Bioequiv Availab, an open access journal
ISSN: 0975-0851
Pharmacy & Biopharma 2017
August 31-September 01, 2017 Philadelphia, USA
August 31-September 01, 2017 Philadelphia, USA
3
rd
International Conference on
Biopharmaceutics and Biologic Drugs
&
5
th
International Pharmacy Conference
J Bioequiv Availab 2017, 9:5 (Suppl)
DOI: 10.4172/0975-0851-C1-031
CHO glycosylation mutant cells as potential hosts for production of therapeutic biologics with enhanced
efficacy
Zhiwei Song
Agency for Science, Technology and Research, Singapore
G
lycosylation can significantly affect the efficacy of recombinant therapeutics. Glycoprotein drugs require a high degree
of sialylation of their N-glycans for a longer circulatory half-life. Mannose-terminated N-glycans can specifically target
the proteins to macrophages and dendritic cells via mannose-binding receptors. Removal of core fucose from human IgG1
has been shown to significantly enhance its affinity to Fc
γ
RIIIa and thereby dramatically improves its antibody-dependent
cellular cytotoxicity (ADCC). Cancer cells generally express glycoproteins with shortened O-glycans. Therefore, recombinant
anti-cancer vaccines carrying these short tumor-associated O-glycans are more ideal for triggering specific anti-tumor
immune responses. With cytotoxic lectins and the newly-developed genome editing technologies, such as ZFNs, TALENs
and CRISPR-Cas9, we have generated more than 20 CHO glycosylation mutant cell lines. Some of these mutant lacks one
specific glycosylation genes whereas others lack more than 10 glycosylation genes. With these CHO cell mutants, we have been
able to produce highly sialylated EPO, recombinant human β-glucocerebrosidase with mannose-terminated N-glycans (like
Cerezyme, but no need for
in vitro
glycan modification) and fucose-free antibodies. Furthermore, these mutant CHO cells
can produce recombinant antibodies carrying different N-glycans with highly homogenous structures (90-97%). These are
invaluable tools for antibody PK/PD studies on the impact of different N-glycans.
song_zhiwei@bti.a-star.edu.sg