Glycoengineering of antibody (Herceptin) through yeast expression and in vitro enzymatic glycosylation

Monoclonal antibodies (mAbs) have been developed as therapeutics, especially for the treatment of cancer, inflammation, and infectious diseases. Because the glycosylation of mAbs in the Fc region influences their interaction with effector cells that kill antibody-targeted cells, and the current meth...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2018-01, Vol.115 (4), p.720-725
Main Authors: Liu, Chiu-Ping, Tsai, Tsung-I., Cheng, Ting, Shivatare, Vidya S., Wu, Chung-Yi, Wong, Chi-Huey
Format: Article
Language:English
Subjects:
Biological Sciences
Cancer
Carbohydrates
Cells
Deglycosylation
Effector cells
Enzymes
Glycosylation
Infectious diseases
Medical treatment
Monoclonal antibodies
Polysaccharides
Substrates
Targeted cancer therapy
Trastuzumab
Yeast
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Summary:Monoclonal antibodies (mAbs) have been developed as therapeutics, especially for the treatment of cancer, inflammation, and infectious diseases. Because the glycosylation of mAbs in the Fc region influences their interaction with effector cells that kill antibody-targeted cells, and the current method of antibody production is relatively expensive, efforts have been directed toward the development of alternative expressing systems capable of large-scale production of mAbs with desirable glycoforms. In this study, we demonstrate that the mAb trastuzumab expressed in glycoengineered P. pastoris can be remodeled through deglycosylation by endoglycosidases identified from the Carbohydrate Active Enzymes database and through transglycosylation using glycans with a stable leaving group to generate a homogeneous antibody designed to optimize the effector functions. The 10 newly identified recombinant bacterial endoglycosidases are complementary to existing endoglycosidases (EndoA, EndoH, EndoS), two of which can even accept sialylated triand tetraantennary glycans as substrates.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1718172115