title: N-Glycosylation Design and Control of Therapeutic Monoclonal Antibodies.
abstract: The N-linked glycan profiles on recombinant monoclonal antibody therapeutics significantly affect antibody biological functions and are largely determined by host cell genotypes and culture conditions. A key step in bioprocess development for monoclonal antibodies (mAbs) involves optimization and control of N-glycan profiles. With pressure from pricing and biosimilars looming, more efficient and effective approaches are sought in the field of glycoengineering. Metabolic studies and mathematical modeling are two such approaches that optimize bioprocesses by better understanding and predicting glycosylation. In this review, we summarize a group of strategies currently used for glycan profile modulation and control. Metabolic analysis and mathematical modeling are then explored with an emphasis on how these two techniques can be utilized to advance glycoengineering.
authors.affiliation: Biomedical Engineering and Biotechnology, University of Massachusetts Lowell, Lowell, MA 01850, USA.
authors.forename: Sha
authors.initials: S
authors.lastname: Sha
authors.affiliation: Division of Biotechnology Review and Research II, Office of Biotechnology Products, OPQ, CDER, FDA, Silver Spring, MD, USA.
authors.forename: Cyrus
authors.initials: C
authors.lastname: Agarabi
authors.affiliation: Division of Biotechnology Review and Research II, Office of Biotechnology Products, OPQ, CDER, FDA, Silver Spring, MD, USA.
authors.forename: Kurt
authors.initials: K
authors.lastname: Brorson
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive, Singapore 117585, Singapore.
authors.forename: Dong-Yup
authors.initials: DY
authors.lastname: Lee
authors.affiliation: Biomedical Engineering and Biotechnology, University of Massachusetts Lowell, Lowell, MA 01850, USA. Electronic address: Seongkyu_Yoon@uml.edu.
authors.forename: Seongkyu
authors.initials: S
authors.lastname: Yoon
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D060847:Metabolic Engineering; D051379:Mice; D011134:Polysaccharides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D011134:Polysaccharides; D011994:Recombinant Proteins
keywords: N-glycosylation; glycoengineering; mathematical modeling; metabolic characterization; monoclonal antibody