The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Efficient generation of stable bispecific IgG1 by controlled Fab-arm exchange
Open accessAbstract
The promise of bispecific antibodies (bsAbs) to yield more effective therapeutics is well recognized; however, the generation of bsAbs in a practical and cost-effective manner has been a formidable challenge. Here we present a technology for the efficient generation of bsAbs with normal IgG structures that is amenable to both antibody drug discovery and development. The process involves separate expression of two parental antibodies, each containing single matched point mutations in the CH3 domains. The parental antibodies are mixed and subjected to controlled reducing conditions in vitro that separate the antibodies into HL half-molecules and allow reassembly and reoxidation to form highly pure bsAbs. The technology is compatible with standard large-scale antibody manufacturing and ensures bsAbs with Fc-mediated effector functions and in vivo stability typical of IgG1 antibodies. Proof-of-concept studies with HER2×CD3 (T-cell recruitment) and HER2×HER2 (dual epitope targeting) bsAbs demonstrate superior in vivo activity compared with parental antibody pairs.
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Cited by
Bispecific antibodies: a mechanistic review of the pipeline
Labrijn, A. F., Janmaat, M. L., Reichert, J. M., & Parren, P. W. H. I. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0028-1 · Cited by 1,303
Self-citationAlternative molecular formats and therapeutic applications for bispecific antibodies
Spiess, C., Zhai, Q., & Carter, P. J. (2015) · Molecular Immunology · doi:10.1016/j.molimm.2015.01.003 · Cited by 607
Bispecific antibodies: design, therapy, perspectives
Sedykh, S., Prinz, V., Buneva, V., & Nevinsky, G. (2018) · Drug Design, Development and Therapy · doi:10.2147/dddt.s151282 · Cited by 292
A review of bispecific antibodies and antibody constructs in oncology and clinical challenges
Suurs, F. V., Lub-de Hooge, M. N., de Vries, E. G. E., & de Groot, D. J. A. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.04.006 · Cited by 292
The Unique Properties of IgG4 and Its Roles in Health and Disease
Rispens, T., & Huijbers, M. G. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-023-00871-z · Cited by 282
Metadata
- Authors
- Labrijn, A. F., Meesters, J. I., de Goeij, B. E. C. G., van den Bremer, E. T. J., Neijssen, J., van Kampen, M. D., Strumane, K., Verploegen, S., Kundu, A., Gramer, M. J., van Berkel, P. H. C., van de Winkel, J. G. J., Schuurman, J., & Parren, P. W. H. I.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2013-03-11
- Volume
- 110
- Issue
- 13
- Pages
- 5145-5150
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2168356942
- Cited by
- 339
- References
- 43
- FWCI
- 17.35
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Labrijn, A. F., Meesters, J. I., de Goeij, B. E. C. G., van den Bremer, E. T. J., Neijssen, J., van Kampen, M. D., Strumane, K., Verploegen, S., Kundu, A., Gramer, M. J., van Berkel, P. H. C., van de Winkel, J. G. J., Schuurman, J., & Parren, P. W. H. I. (2013). Efficient generation of stable bispecific IgG1 by controlled Fab-arm exchange. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1220145110
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
