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Int. J. Mol. Sci. 2018, 19(2), 421; doi:10.3390/ijms19020421

Implementation of Glycan Remodeling to Plant-Made Therapeutic Antibodies

1
Metropolitan Nashville Police Department Crime Lab, 400 Myatt Drive, Madison, TN 37115, USA
2
Department of Chemistry and Biochemistry, University of Maryland, 8051 Regents Drive, College Park, MD 20742, USA
3
iBio CDMO, 8800 Health Science Center Parkway, Bryan, TX 77807, USA
4
Lonza Houston, Inc., 8066 El Rio St., Houston, TX 77054, USA
5
MDx BioAnalytical Laboratory, Inc., 5890 Imperial loop, Suite 12, College Station, TX 77845, USA
*
Authors to whom correspondence should be addressed.
Received: 2 December 2017 / Revised: 9 January 2018 / Accepted: 27 January 2018 / Published: 31 January 2018
(This article belongs to the Special Issue Recombinant Proteins)
View Full-Text   |   Download PDF [2674 KB, uploaded 31 January 2018]   |  

Abstract

N-glycosylation profoundly affects the biological stability and function of therapeutic proteins, which explains the recent interest in glycoengineering technologies as methods to develop biobetter therapeutics. In current manufacturing processes, N-glycosylation is host-specific and remains difficult to control in a production environment that changes with scale and production batches leading to glycosylation heterogeneity and inconsistency. On the other hand, in vitro chemoenzymatic glycan remodeling has been successful in producing homogeneous pre-defined protein glycoforms, but needs to be combined with a cost-effective and scalable production method. An efficient chemoenzymatic glycan remodeling technology using a plant expression system that combines in vivo deglycosylation with an in vitro chemoenzymatic glycosylation is described. Using the monoclonal antibody rituximab as a model therapeutic protein, a uniform Gal2GlcNAc2Man3GlcNAc2 (A2G2) glycoform without α-1,6-fucose, plant-specific α-1,3-fucose or β-1,2-xylose residues was produced. When compared with the innovator product Rituxan®, the plant-made remodeled afucosylated antibody showed similar binding affinity to the CD20 antigen but significantly enhanced cell cytotoxicity in vitro. Using a scalable plant expression system and reducing the in vitro deglycosylation burden creates the potential to eliminate glycan heterogeneity and provide affordable customization of therapeutics’ glycosylation for maximal and targeted biological activity. This feature can reduce cost and provide an affordable platform to manufacture biobetter antibodies. View Full-Text
Keywords: glycan remodeling; therapeutic proteins; recombinant glycoproteins; Nicotiana benthamiana; N-glycosylation glycan remodeling; therapeutic proteins; recombinant glycoproteins; Nicotiana benthamiana; N-glycosylation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Bennett, L.D.; Yang, Q.; Berquist, B.R.; Giddens, J.P.; Ren, Z.; Kommineni, V.; Murray, R.P.; White, E.L.; Holtz, B.R.; Wang, L.-X.; Marcel, S. Implementation of Glycan Remodeling to Plant-Made Therapeutic Antibodies. Int. J. Mol. Sci. 2018, 19, 421.

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