Characterization of alanine to valine sequence variants in the Fc region of nivolumab biosimilar produced in Chinese hamster ovary cells

Li, Yantao; Fu, Tuo; Liu, Tao; Guo, Haipeng; Guo, Qingcheng; Xu, Jin; Zhang, David; Qian, Weizhu; Dai, Jing; Li, Bohua; Guo, Yajun; Hou, Sheng; Wang, Hao

doi:10.1080/19420862.2016.1172150

Cited by 13 publications

(9 citation statements)

References 39 publications

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“…Thus, peptide mapping is also a valuable tool for evaluating the stability of reference standards. When coupled with mass spectrometry, changes in the landscape of the map can be pinpointed to a particular attribute, such as increased oxidation of a certain methionine residue [ 2 – 5 ] appearance of a new sequence variant [ 6 – 9 ] or changes in glycan composition [ 10 – 12 ]. These principles also apply to the use of peptide mapping techniques for the purposes of assessing biosimilarity to an originator drug product [ 13 – 19 ].…”

Section: Introductionmentioning

confidence: 99%

Development of an LC-MS/MS peptide mapping protocol for the NISTmAb

2018

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Peptide mapping is a component of the analytical toolbox used within the biopharmaceutical industry to aid in the identity confirmation of a protein therapeutic and to monitor degradative events such as oxidation or deamidation. These methods offer the advantage of providing site-specific information regarding post-translational and chemical modifications that may arise during production, processing or storage. A number of such variations may also be induced by the sample preparation methods themselves which may confound the ability to accurately evaluate the true modification levels. One important focus when developing a peptide mapping method should therefore be the use of sample preparation conditions that will minimize the degree of artificial modifications induced. Unfortunately, the conditions that are amenable to effective reduction, alkylation and digestion are often the same conditions that promote unwanted modifications. Here we describe the optimization of a tryptic digestion protocol used for peptide mapping of the NISTmAb IgG1κ which addresses the challenge of balancing maximum digestion efficiency with minimum artificial modifications. The parameters on which we focused include buffer concentration, digestion time and temperature, as well as the source and type of trypsin (recombinant vs. pancreatic; bovine vs porcine) used. Using the optimized protocol we generated a peptide map of the NISTmAb which allowed us to confirm its identity at the level of primary structure. Graphical abstractPeptide map of the NISTmAb RM 8671 monoclonal antibody. Tryptic digestion was performed using an optimized protocol and followed by LC-UV-MS analysis. The trace represents the total ion chromatogram. Each peak was mapped to peptides identified using mass spectrometry data. Electronic supplementary materialThe online version of this article (10.1007/s00216-018-0848-6) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Development of an LC-MS/MS peptide mapping protocol for the NISTmAb

2018

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“…We tested the potential validity of using LC-tandem mass spectrometry in the determination process for the similarity of biosimilar products to the reference materials in biosimilar samples with a single mutation in amino acid sequences. Unintentional mutations that arise during protein production can cause changes in glycosylation patterns, which in turn can impact the safety, quality, and potency of the recombinant rAbs [ 28 ]. A tryptophan to valine amino acid mutation was created in the vicinity of the glycosylation site of Adalimumab to test its effect on the pattern of glycosylation to be detected using LC-tandem mass spectrometry.…”

Section: Resultsmentioning

confidence: 99%

Comparative Glycopeptide Analysis for Protein Glycosylation by Liquid Chromatography and Tandem Mass Spectrometry: Variation in Glycosylation Patterns of Site-Directed Mutagenized Glycoprotein

Hahm¹,

Hahm²,

Jo³

et al. 2018

International Journal of Analytical Chemistry

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Glycosylation is one of the most important posttranslational modifications for proteins, including therapeutic antibodies, and greatly influences protein physiochemical properties. In this study, glycopeptide mapping of a reference and biosimilar recombinant antibodies (rAbs) was performed using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) and an automated Glycoproteome Analyzer (GPA) algorithm. The tandem mass analyses for the reference and biosimilar samples indicate that this approach proves to be highly efficient in reproducing consistent analytical results and discovering the implications of different rAb production methods on glycosylation patterns. Furthermore, the comparative analysis of a mutagenized rAb glycoprotein proved that a single amino acid mutation in the Fc portion of the antibody molecule caused increased variations in glycosylation patterns. These variations were also detected by the mass spectrometry method efficiently. This mapping method, focusing on precise glycopeptide identification and comparison for the identified glycoforms, can be useful in differentiating aberrant glycosylation in biosimilar rAb products.

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“…Nivolumab is a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody which is approved in NSCLC in 2015 [25,30]. It can disrupt the negative signal that mediates T-cell activation and proliferation via binding to PD-1 on activated immune cells in order to selectively block the interaction of the PD-1 receptor with its two programmed death ligands (PD-L1 and PD-L2) [30]. Nivolumab was active in advanced NSCLC in first-and second-line settings.…”

Section: Nivolumabmentioning

confidence: 99%

Monoclonal antibodies in non-small-cell lung cancer: Light at the end of the tunnel

Naddafi¹

2019

Trends Med

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Lung cancer is the leading cause of death and non-small cell lung cancer (NSCLC) is considered as the most common type of lung cancer. Several conventional therapies, such as surgery, radiation, and chemotherapy are used for the treatment of lung cancer. But, these therapies could have multiple undesirable side effects. Therefore, there is an urgent need for therapeutic agents to improve the clinical outcomes for cases with NSCLC. Recently, therapeutic antibodies have shown promise for NSCLC treatment. The aim of this review is to discuss FDA-approved antibodies such as durvalumab, pembrolizumab, necitumumab and nivolumab in the treatment of NSCLC as well as Onartuzumab, a monoclonal antibody against c-MET, that was discontinued due to its lack of clinical activity. Furthermore, the aim of this manuscript is to give a brief overview about NSCLC therapeutic mAbs.

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Characterization of alanine to valine sequence variants in the Fc region of nivolumab biosimilar produced in Chinese hamster ovary cells

Cited by 13 publications

References 39 publications

Development of an LC-MS/MS peptide mapping protocol for the NISTmAb

Development of an LC-MS/MS peptide mapping protocol for the NISTmAb

Comparative Glycopeptide Analysis for Protein Glycosylation by Liquid Chromatography and Tandem Mass Spectrometry: Variation in Glycosylation Patterns of Site-Directed Mutagenized Glycoprotein

Monoclonal antibodies in non-small-cell lung cancer: Light at the end of the tunnel

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