Implementation of Glycan Remodeling to Plant-Made Therapeutic Antibodies

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dc.contributor.authorBennett, Lindsay D.
dc.contributor.authorYang, Qiang
dc.contributor.authorBerquist, Brian R.
dc.contributor.authorGiddens, John P.
dc.contributor.authorRen, Zhongjie
dc.contributor.authorKommineni, Vally
dc.contributor.authorMurray, Ryan P.
dc.contributor.authorWhite, Earl L.
dc.contributor.authorHoltz, Barry R.
dc.contributor.authorWang, Lai-Xi
dc.contributor.authorMarcel, Sylvain
dc.date.accessioned2023-11-28T15:04:43Z
dc.date.available2023-11-28T15:04:43Z
dc.date.issued2018-01-31
dc.description.abstractN-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.
dc.description.urihttps://doi.org/10.3390/ijms19020421
dc.identifierhttps://doi.org/10.13016/dspace/6mgg-cvcf
dc.identifier.citationBennett, 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.; et al. Implementation of Glycan Remodeling to Plant-Made Therapeutic Antibodies. Int. J. Mol. Sci. 2018, 19, 421.
dc.identifier.urihttp://hdl.handle.net/1903/31486
dc.language.isoen_US
dc.publisherMDPI
dc.relation.isAvailableAtDigital Repository at the University of Marylanden_us
dc.relation.isAvailableAtChemistry & Biochemistryen_us
dc.relation.isAvailableAtCollege of Computer, Mathematical & Natural Sciencesen_us
dc.relation.isAvailableAtUniversity of Maryland (College Park, MD)en_us
dc.subjectglycan remodeling
dc.subjecttherapeutic proteins
dc.subjectrecombinant glycoproteins
dc.subjectNicotiana benthamiana
dc.subjectN-glycosylation
dc.titleImplementation of Glycan Remodeling to Plant-Made Therapeutic Antibodies
dc.typeArticle
local.equitableAccessSubmissionNo

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