ArticleProtein science : a publication of the Protein Society2017
Computational design of a specific heavy chain/κ light chain interface for expressing fully IgG bispecific antibodies.
Article in Protein science : a publication of the Protein Society, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Deep generative modeling captures maturation-dependent pairing patterns in human antibodies.iScience · 2026Article
- Bispecific antibodies targeting herpes simplex virus glycoproteins B and D.Frontiers in immunology · 2026Article
- Article
- Addressing epistasis in the design of protein function.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- BiSpec Pairwise AI: guiding the selection of bispecific antibody target combinations with pairwise learning and GPT augmentation.Journal of cancer research and clinical oncology · 2024Article
- A Novel Dual-Fc Bispecific Antibody with Enhanced Fc Effector Function.Biochemistry · 2024Article
- Design and engineering of bispecific antibodies: insights and practical considerations.Frontiers in bioengineering and biotechnology · 2024Review
- Modeling Immunity with Rosetta: Methods for Antibody and Antigen Design.Biochemistry · 2021Review
- Crystal Structure and Characterization of Human Heavy-Chain Only Antibodies Reveals a Novel, Stable Dimeric Structure Similar to Monoclonal Antibodies.Antibodies (Basel, Switzerland) · 2020Article
- 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
- Computational stabilization of T cell receptors allows pairing with antibodies to form bispecifics.Nature communications · 2020Article
- Biology drives the discovery of bispecific antibodies as innovative therapeutics.Antibody therapeutics · 2020Review
- Designing protein structures and complexes with the molecular modeling program Rosetta.The Journal of biological chemistry · 2019Review
- Advances in protein structure prediction and design.Nature reviews. Molecular cell biology · 2019Review
- Article
- Engineering IgG-Like Bispecific Antibodies-An Overview.Antibodies (Basel, Switzerland) · 2018Review
- Article
- Engineering a tumor-selective prodrug T-cell engager bispecific antibody for safer immunotherapy.mAbsArticle
- Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
The use of bispecific antibodies (BsAbs) to treat human diseases is on the rise. Increasingly complex and powerful therapeutic mechanisms made possible by BsAbs are spurring innovation of novel BsAb formats and methods for their production. The long-lived in vivo pharmacokinetics, optimal biophysical properties and potential effector functions of natural IgG monoclonal (and monospecific) antibodies has resulted in a push to generate fully IgG BsAb formats with the same quaternary structure as monoclonal IgGs. The production of fully IgG BsAbs is challenging because of the highly heterogeneous pairing of heavy chains (HCs) and light chains (LCs) when produced in mammalian cells with two IgG HCs and two LCs. A solution to the HC heterodimerization aspect of IgG BsAb production was first discovered two decades ago; however, addressing the LC mispairing issue has remained intractable until recently. Here, we use computational and rational engineering to develop novel designs to the HC/LC pairing issue, and particularly for κ LCs. Crystal structures of these designs highlight the interactions that provide HC/LC specificity. We produce and characterize multiple fully IgG BsAbs using these novel designs. We demonstrate the importance of specificity engineering in both the variable and constant domains to achieve robust HC/LC specificity within all the BsAbs. These solutions facilitate the production of fully IgG BsAbs for clinical use.
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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.