Beyond bispecificity: Controlled Fab arm exchange for the generation of antibodies with multiple specificities
| Autor: | Desislava Yanakieva, Lukas Pekar, Andreas Evers, Markus Fleischer, Stephan Keller, Dirk Mueller-Pompalla, Lars Toleikis, Harald Kolmar, Stefan Zielonka, Simon Krah |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | mAbs, Vol 14, Iss 1 (2022) |
| Druh dokumentu: | article |
| ISSN: | 1942-0862 1942-0870 19420862 |
| DOI: | 10.1080/19420862.2021.2018960 |
| Popis: | Controlled Fab arm exchange (cFAE) has proven to be a generic and versatile technology for the efficient generation of IgG-like bispecific antibodies (DuoBodies or DBs), with several in clinical development and one product, amivantamab, approved by the Food and Drug Administration. In this study, we expand the cFAE-toolbox by incorporating VHH-modules at the C-termini of DB-IgGs, termed DB-VHHs. This approach enables the combinatorial generation of tri- and tetraspecific molecules with flexible valencies in a straightforward fashion. Using cFAE, a variety of multispecific molecules was produced and assessed for manufacturability and physicochemical characteristics. In addition, we were able to generate DB-VHHs that efficiently triggered natural killer cell mediated lysis of tumor cells, demonstrating the utility of this format for potential therapeutic applications. |
| Databáze: | Directory of Open Access Journals |
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