ArticleThe Journal of biological chemistry2015
A novel antibody engineering strategy for making monovalent bispecific heterodimeric IgG antibodies by electrostatic steering mechanism.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 74 citations in OpenAlex.
- Folding-mediated secretion of pure bispecific antibodies.Nature biotechnology · 2026Article
- Generation of mixed-valency, modular multispecific antibodies using disulfide-linked Fc-FcγR complexes.Nature communications · 2026Article
- Generation of Bispecific Antibodies Using FAST-Ig™.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Comparison of enriched charge variants from different anti-CD3 bispecific antibodies reveals differential susceptibility of each bispecific arm to post-translational modification.Protein science : a publication of the Protein Society · 2025Article
- Unveiling the Synergistic Potential: Bispecific Antibodies in Conjunction with Chemotherapy for Advanced Non-Small-Cell Lung Cancer Treatment.Current oncology (Toronto, Ont.) · 2025Review
- An Engineered Mouse Model That Generates a Diverse Repertoire of Endogenous, High-Affinity Common Light Chain Antibodies.Antibodies (Basel, Switzerland) · 2024Article
- Design and engineering of bispecific antibodies: insights and practical considerations.Frontiers in bioengineering and biotechnology · 2024Review
- Fc-Engineered Therapeutic Antibodies: Recent Advances and Future Directions.Pharmaceutics · 2023Review
- Cattle-derived knob paratopes grafted onto peripheral loops of the IgG1 Fc region enable the generation of a novel symmetric bispecific antibody format.Frontiers in immunology · 2023Article
- Next generation Fc scaffold for multispecific antibodies.iScience · 2021Article
- A new immunochemical strategy for triple-negative breast cancer therapy.Scientific reports · 2021Article
- Bioanalysis in the Age of New Drug Modalities.The AAPS journal · 2021Review
- Recent Advances in the Molecular Design and Applications of Multispecific Biotherapeutics.Antibodies (Basel, Switzerland) · 2021Review
- Bringing the Heavy Chain to Light: Creating a Symmetric, Bivalent IgG-Like Bispecific.Antibodies (Basel, Switzerland) · 2020Article
- Toward Drug-Like Multispecific Antibodies by Design.International journal of molecular sciences · 2020Review
- High-Throughput Generation of Bipod (Fab × scFv) Bispecific Antibodies Exploits Differential Chain Expression and Affinity Capture.Scientific reports · 2020Article
- Biology drives the discovery of bispecific antibodies as innovative therapeutics.Antibody therapeutics · 2020Review
- Antibody Structure and Function: The Basis for Engineering Therapeutics.Antibodies (Basel, Switzerland) · 2019Review
- Article
- Immunoglobulin Gamma-Like Therapeutic Bispecific Antibody Formats for Tumor Therapy.Journal of immunology research · 2019Review
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Producing pure and well behaved bispecific antibodies (bsAbs) on a large scale for preclinical and clinical testing is a challenging task. Here, we describe a new strategy for making monovalent bispecific heterodimeric IgG antibodies in mammalian cells. We applied an electrostatic steering mechanism to engineer antibody light chain-heavy chain (LC-HC) interface residues in such a way that each LC strongly favors its cognate HC when two different HCs and two different LCs are co-expressed in the same cell to assemble a functional bispecific antibody. We produced heterodimeric IgGs from transiently and stably transfected mammalian cells. The engineered heterodimeric IgG molecules maintain the overall IgG structure with correct LC-HC pairings, bind to two different antigens with comparable affinity when compared with their parental antibodies, and retain the functionality of parental antibodies in biological assays. In addition, the bispecific heterodimeric IgG derived from anti-HER2 and anti-EGF receptor (EGFR) antibody was shown to induce a higher level of receptor internalization than the combination of two parental antibodies. Mouse xenograft BxPC-3, Panc-1, and Calu-3 human tumor models showed that the heterodimeric IgGs strongly inhibited tumor growth. The described approach can be used to generate tools from two pre-existent antibodies and explore the potential of bispecific antibodies. The asymmetrically engineered Fc variants for antibody-dependent cellular cytotoxicity enhancement could be embedded in monovalent bispecific heterodimeric IgG to make best-in-class therapeutic antibodies.
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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.