Isotype and glycoform selection for antibody therapeutics

Jefferis, Royston

doi:10.1016/j.abb.2012.03.021

Cited by 218 publications

(173 citation statements)

References 120 publications

Supporting

Mentioning

171

Contrasting

Order By: Relevance

“…mAbs are always a mixture of different glycosylated forms. 35 This is important when considering biosimilar products because different cell lines or culture conditions can modify the glycosylation of the antibodies produced, and, therefore, also their Fc-mediated functionality. 36 Indeed, removal of fucose, as is the case with obinutuzumab, results in an increase in its affinity for the FcγRIIIA receptor and increased ADCC.…”

Section: -34mentioning

confidence: 99%

“…Therefore, the Asn297 glycosylation does not affect significantly the half-life of the antibody in vivo. 35 Finally, C1q binding and CDC may be affected by the glycosylation pattern of IgG1 antibodies, but is not significantly modified by defucosylation [38][39][40] Rituximab PK Doses and routes of administration. RTX is usually administered by intravenous (i.v.)…”

Section: -34mentioning

confidence: 99%

See 1 more Smart Citation

Lessons for the clinic from rituximab pharmacokinetics and pharmacodynamics

Golay

Semenzato

Rambaldi

et al. 2013

mAbs

115

View full text Add to dashboard Cite

Section: -34mentioning

confidence: 99%

Section: -34mentioning

confidence: 99%

Lessons for the clinic from rituximab pharmacokinetics and pharmacodynamics

Golay

Semenzato

Rambaldi

et al. 2013

mAbs

115

View full text Add to dashboard Cite

“…Glycosylation is the most important post-translational modification for many reasons. Firstly, glycosylation alters the properties of proteins, including pharmacokinetics, 10 pharmacodistribution, 11 effector function, 12 antigenicity, 13 solubility, 14 and stability. 15 After years of research, we now know that glycosylation can be influenced by cell lines, conformation of proteins, and cell culture conditions.…”

Section: Introductionmentioning

confidence: 99%

Versatile characterization of glycosylation modification in CTLA4-Ig fusion proteins by liquid chromatography-mass spectrometry

Zhu

Guo

Guo³

et al. 2014

mAbs

View full text Add to dashboard Cite

These authors contributed equally to this work.Keywords: characterization, CTLA4-Ig fusion protein, glycan, glycosylation modification, intact protein, mass spectrometry, peptide mapping, similarity CTLA4-Ig is a highly glycosylated therapeutic fusion protein that contains multiple N-and O-glycosylation sites. Glycosylation plays a vital role in protein solubility, stability, serum half-life, activity, and immunogenicity. For a CTLA4-Ig biosimilar development program, comparative analytical data, especially the glycosylation data, can influence decisions about the type and amount of animal and clinical data needed to establish biosimilarity. Because of the limited clinical experience with biosimilars before approval, a comprehensive level of knowledge about the biosimilar candidates is needed to achieve subsequent development. Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N-and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. In this report, an in-depth characterization of glycosylation of a candidate biosimilar was carried out using a systematic approach: N-and O-linked glycans were identified and electron-transfer dissociation was then used to pinpoint the 4 occupied O-glycosylation sites for the first time. As the results show, the approach provides a set of routine tools that combine accurate intact mass measurement, peptide mapping, and released glycan profiling. This approach can be used to comprehensively research a candidate biosimilar Fc-fusion protein and provides a basis for future studies addressing the similarity of CTLA4-Ig biosimilars.

show abstract

“…An Ig is a "dimer of a dimer" consisting of light chains and heavy chains in which each light chain is linked to a heavy chain and the light-heavy dimers are connected by disulfide bridges to form the intact antibody. IgG is the most prevalent Ig isotype in plasma and is the most commonly used isotype for therapeutic antibodies because of its strong ability to induce antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity (2). The IgG 1 subtype is a 150 kDa Y-shaped glycoprotein.…”

mentioning

confidence: 99%