A novel efficient bispecific antibody format, combining a conventional antigen-binding fragment with a single domain antibody, avoids potential heavy-light chain mis-pairing
Huang S, Segues A, Hulsik DL, Zaiss DM, Sijts AJAM, Van Duijnhoven SMJ, Van Elsas A (2020)
Publication Type: Journal article
Publication year: 2020
Journal
Book Volume: 483
Article Number: 112811
DOI: 10.1016/j.jim.2020.112811
Abstract
Due to the technical innovations in generating bispecific antibodies (BsAbs) in recent years, BsAbs have become important reagents for diagnostic and therapeutic applications. However, the difficulty of producing a heterodimer consisting of two different arms with high yield and purity constituted a major limitation for their application in academic and clinical settings. Here, we describe a novel Fc-containing BsAb format (Fab × sdAb-Fc) composed of a conventional antigen-binding fragment (Fab), and a single domain antibody (sdAb), which avoids heavy-light chain mis-pairing during antibody assembly. In this study, the Fab x sdAb-Fc BsAbs were efficiently produced by three widely used heavy-heavy chain heterodimerization methods: Knobs-into-holes (KIH), Charge-pairs (CP) and controlled Fab-arm exchange (cFAE), respectively. The novel Fab x sdAb-Fc format provided a rapid and efficient strategy to generate BsAb with high purity and a unique possibility to further purify desired BsAbs from undesired antibodies based on molecular weight (MW). Compared to conventional BsAb formats, the advantages of Fab x sdAb-Fc format may thus provide a straightforward opportunity to apply bispecific antibody principles to research and development of novel targets and pathways in diseases such as cancer and autoimmunity.
Involved external institutions
Aduro Biotech Holding, Europe B.V.
Netherlands (NL)
University of Edinburgh
United Kingdom (GB)
Universiteit Utrecht (UU) / Utrecht University
Netherlands (NL)
Netherlands (NL)
University of Edinburgh
United Kingdom (GB)
Universiteit Utrecht (UU) / Utrecht University
Netherlands (NL)
How to cite
APA:
Huang, S., Segues, A., Hulsik, D.L., Zaiss, D.M., Sijts, A.J.A.M., Van Duijnhoven, S.M.J., & Van Elsas, A. (2020). A novel efficient bispecific antibody format, combining a conventional antigen-binding fragment with a single domain antibody, avoids potential heavy-light chain mis-pairing. Journal of Immunological Methods, 483. https://doi.org/10.1016/j.jim.2020.112811
MLA:
Huang, Shuyu, et al. "A novel efficient bispecific antibody format, combining a conventional antigen-binding fragment with a single domain antibody, avoids potential heavy-light chain mis-pairing." Journal of Immunological Methods 483 (2020).
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