ArticleScientific reports2018
Engineering the hinge region of human IgG1 Fc-fused bispecific antibodies to improve fragmentation resistance.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Single injection of modified self-amplifying RNA encoding a CD19 bispecific T cell engager mediates long-term malignant B cell clearance.bioRxiv : the preprint server for biology · 2026Article
- Bispecific Antibodies in B-Cell Lymphomas: Mechanisms, Efficacy, Toxicity, and Management.Medicina (Kaunas, Lithuania) · 2026Review
- Production of Bispecific Antibody Fragments from Fc Fusion.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Design of a prodrug bispecific antibody masked by a functional molecule for lymphocyte activation for cancer therapy.Journal of biological engineering · 2025Article
- Stability of Protein Pharmaceuticals: Recent Advances.Pharmaceutical research · 2024Review
- A structural peculiarity of Antarctic fish IgM drives the generation of an engineered mAb by CRISPR/Cas9.Frontiers in bioengineering and biotechnology · 2024Article
- Generation and characterization of OX40-ligand fusion protein that agonizes OX40 on T-Lymphocytes.Frontiers in immunology · 2024Article
- Protein PEGylation: Navigating Recombinant Protein Stability, Aggregation, and Bioactivity.BioMed research international · 2022Review
- Immunotherapy of Multiple Myeloma: Promise and Challenges.ImmunoTargets and therapy · 2021Review
- Mechanism of action of a T cell-dependent bispecific antibody as a breakthrough immunotherapy against refractory colorectal cancer with an oncogenic mutation.Cancer immunology, immunotherapy : CII · 2021Article
- Large-scale production, purification, and function of a tumor multi-epitope vaccine: Peptibody with bFGF/VEGFA.Engineering in life sciences · 2020Article
- B-Cell Maturation Antigen (BCMA) as a Target for New Drug Development in Relapsed and/or Refractory Multiple Myeloma.International journal of molecular sciences · 2020Review
- Direct Blood Culturing ofJournal of clinical microbiology · 2020Article
- The Design, Characterizations, and Tumor Angiogenesis Inhibition of a Multi-Epitope Peptibody With bFGF/VEGFA.Frontiers in oncology · 2020Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fc domain fusion can improve the therapeutic effects of relatively small biological molecules such as peptides, cytokines, and antibody fragments. Fc fusion proteins can also be used to enhance the cytotoxic effects of small bispecific antibodies (bsAbs). However, fragmentation of Fc fusion proteins, which mainly occurs around the hinge regions during production, storage, and circulation in the blood, is a major issue. In this study, we first investigated the mechanisms of fragmentation around the hinge region during storage using Fc-fused bsAbs with specificity for epidermal growth factor receptor and CD3 as a model. The fragmentation peaks generated by gel filtration analysis indicated that both contaminating proteases and dissolved active oxygen should be considered causes of fragmentation. We designed and constructed variants by introducing a point mutation into the upper hinge region, which reduced the cleavage caused by dissolved active oxygen, and shortened the hinge region to restrict access of proteases. These hinge modifications improved fragmentation resistance and did not affect the biological activity of the bsAbs in vitro. We confirmed the versatility of the hinge modifications using another Fc-fused bsAb. Our results show that hinge modifications to the Fc fusion protein, especially the introduction of a point mutation into the upper hinge region, can reduce fragmentation substantially, and these modifications can be used to improve the fragmentation resistance of other recombinant Fc fusion proteins.
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