ArticlemAbs
Characterization and analysis of scFv-IgG bispecific antibody size variants.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Functional Characteristics Derived from the Structural Design of Bispecific Antibodies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- The Production and Purification of Therapeutic Antibodies: A Comprehensive Analysis of Process- and Product-Related Contaminants.Biomolecules · 2026Review
- Engineering and physicochemical characterization of a novel, stable, symmetric bispecific antibody with dual target-binding using a common light chain.Protein science : a publication of the Protein Society · 2024Article
- Design and engineering of bispecific antibodies: insights and practical considerations.Frontiers in bioengineering and biotechnology · 2024Review
- Heterogeneity in Disulfide Bond Reduction in IgG1 Antibodies Is Governed by Solvent Accessibility of the Cysteines.Antibodies (Basel, Switzerland) · 2023Article
- Bispecific antibody targeting both B7-H3 and PD-L1 exhibits superior antitumor activities.Acta pharmacologica Sinica · 2023Article
- Construction and stable gene expression of AGR2xPD1 bi-specific antibody that enhances attachment betweenSaudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Article
- HER2/PD1 bispecific antibody in IgG4 subclass with superior anti-tumour activities.Clinical and translational medicine · 2022Article
- Structural design of tetravalent T-cell engaging bispecific antibodies: improve developability by engineering disulfide bonds.Journal of biological engineering · 2021Article
- Bioanalysis in the Age of New Drug Modalities.The AAPS journal · 2021Review
- Toward Drug-Like Multispecific Antibodies by Design.International journal of molecular sciences · 2020Review
- Perfusion reduces bispecific antibody aggregation via mitigating mitochondrial dysfunction-induced glutathione oxidation and ER stress in CHO cells.Scientific reports · 2020Article
- Impact of enzymatic reduction on bivalent bispecific antibody fragmentation and loss of product purity upon reoxidation.Biotechnology and bioengineering · 2020Article
- Amber suppression coupled with inducible surface display identifies cells with high recombinant protein productivity.Biotechnology and bioengineering · 2019Article
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bispecific antibodies are an emergent class of biologics that is of increasing interest for therapeutic applications. In one bispecific antibody format, single-chain variable fragments (scFv) are linked to or inserted in different locations of an intact immunoglobulin G (IgG) molecule to confer dual epitope binding. To improve biochemical stability, cysteine residues are often engineered on the heavy- and light-chain regions of the scFv to form an intrachain disulfide bond. Although this disulfide bond often improves stability, it can also introduce unexpected challenges to manufacturing or development. We report size variants that were observed for an appended scFv-IgG bispecific antibody. Structural characterization studies showed that the size variants resulted from the engineered disulfide bond on the scFv, whereby the engineered disulfide was found to be either open or unable to form an intrachain disulfide bond due to cysteinylation or glutathionylation of the cysteines. Furthermore, the scFv engineered cysteines also formed intermolecular disulfide bonds, leading to the formation of highly stable dimers and aggregates. Because both the monomer variants and dimers showed lower bioactivity, they were considered to be product-related impurities that must be monitored and controlled. To this end, we developed and optimized a robust, precise, and accurate high-resolution size-exclusion chromatographic method, using a statistical design-of-experiments methodology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.