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Importance and Monitoring of Therapeutic Immunoglobulin G Glycosylation.
Mimura, Yusuke; Saldova, Radka; Mimura-Kimura, Yuka; Rudd, Pauline M; Jefferis, Roy.
Afiliación
  • Mimura Y; Department of Clinical Research, National Hospital Organization Yamaguchi Ube Medical Center, Ube, Japan. mimura.yusuke.qy@mail.hosp.go.jp.
  • Saldova R; NIBRT GlycoScience Group, National Institute for Bioprocessing Research and Training, Mount Merrion, Blackrock, Dublin, Ireland.
  • Mimura-Kimura Y; UCD School of Medicine, College of Health and Agricultural Science, University College Dublin, Belfield, Dublin, Ireland.
  • Rudd PM; Department of Clinical Research, National Hospital Organization Yamaguchi Ube Medical Center, Ube, Japan.
  • Jefferis R; NIBRT GlycoScience Group, National Institute for Bioprocessing Research and Training, Mount Merrion, Blackrock, Dublin, Ireland.
Exp Suppl ; 112: 481-517, 2021.
Article en En | MEDLINE | ID: mdl-34687020
The complex diantennary-type oligosaccharides at Asn297 residues of the IgG heavy chains have a profound impact on the safety and efficacy of therapeutic IgG monoclonal antibodies (mAbs). Fc glycosylation of a mAb is an established critical quality attribute (CQA), and its oligosaccharide profile is required to be thoroughly characterized by state-of-the-art analytical methods. The Fc oligosaccharides are highly heterogeneous, and the differentially glycosylated species (glycoforms) of IgG express unique biological activities. Glycoengineering is a promising approach for the production of selected mAb glycoforms with improved effector functions, and non- and low-fucosylated mAbs exhibiting enhanced antibody-dependent cellular cytotoxicity activity have been approved or are under clinical evaluation for treatment of cancers, autoimmune/chronic inflammatory diseases, and infection. Recently, the chemoenzymatic glycoengineering method that allows for the transfer of structurally defined oligosaccharides to Asn-linked GlcNAc residues with glycosynthase has been developed for remodeling of IgG-Fc oligosaccharides with high efficiency and flexibility. Additionally, various glycoengineering methods have been developed that utilize the Fc oligosaccharides of IgG as reaction handles to conjugate cytotoxic agents by "click chemistry", providing new routes to the design of antibody-drug conjugates (ADCs) with tightly controlled drug-antibody ratios (DARs) and homogeneity. This review focuses on current understanding of the biological relevance of individual IgG glycoforms and advances in the development of next-generation antibody therapeutics with improved efficacy and safety through glycoengineering.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inmunoglobulina G / Anticuerpos Monoclonales Idioma: En Revista: Exp Suppl Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inmunoglobulina G / Anticuerpos Monoclonales Idioma: En Revista: Exp Suppl Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza