Trends in Glycosylation, Glycoanalysis and Glycoengineering of Therapeutic Antibodies and Fc-Fusion Proteins

被引:183
作者
Beck, Alain [1 ]
Wagner-Rousset, Elsa [1 ]
Bussat, Marie-Claire [1 ]
Lokteff, Maryline [1 ]
Klinguer-Hamour, Christine [1 ]
Haeuw, Jean-Francois [1 ]
Goetsch, Liliane [1 ]
Wurch, Thierry [1 ]
Van Dorsselaer, Alain [2 ]
Corvaia, Nathalie [1 ]
机构
[1] Ctr Immunol Pierre Fabre, F-74160 St Julien En Genevois, France
[2] ULP, CNRS, LSMBO, IPHC DSA,UMR7178, F-67087 Strasbourg, France
关键词
Therapeutic antibody; Fc-fusion protein; mass spectrometry; capillary electrophoresis; glycoengineering; glycomics; glycoanalytics;
D O I
10.2174/138920108786786411
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Monoclonal antibodies (MAbs) are the fastest growing class of human pharmaceuticals. More than 20 MAbs have been approved and several hundreds are in clinical trials in various therapeutic indications including oncology, inflammatory diseases, organ transplantation, cardiology, viral infection, allergy, and tissue growth and repair. Most of the current therapeutic antibodies are humanized or human Immunoglobulins (IgGs) and are produced as recombinant glycoproteins in eukaryotic cells. Many alternative production systems and improved constructs are also being actively investigated. IgGs glycans represent only an average of around 3 % of the total mass of the molecule. Despite this low percentage, particular glycoforms are involved in essential immune effector functions. On the other hand, glycoforms that are not commonly biosynthesized in human may be allergenic, immunogenic and accelerate the plasmatic clearance of the linked antibody. These glyco-variants have to be identified, controlled and limited for therapeutic uses. Glycosylation depends on multiple factors like production system, selected clonal population, manufacturing process and may be genetically or chemically engineered. The present account reviews the glycosylation patterns observed for the current approved therapeutic antibodies produced in mammalian cell lines, details classical and state-of-the-art analytical methods used for the characterization of glycoforms and discusses the expected benefits of manipulating the carbohydrate components of antibodies by bio- or chemical engineering as well as the expected advantages of alternative biotechnological production systems developed for new generation of therapeutic antibodies and Fc-fusion proteins.
引用
收藏
页码:482 / 501
页数:20
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