Beyond bispecificity: Controlled Fab arm exchange for the generation of antibodies with multiple specificities

• Main Authors: Desislava Yanakieva (Author), Lukas Pekar (Author), Andreas Evers (Author), Markus Fleischer (Author), Stephan Keller (Author), Dirk Mueller-Pompalla (Author), Lars Toleikis (Author), Harald Kolmar (Author), Stefan Zielonka (Author), Simon Krah (Author)
• Format: Book
• Published: Taylor & Francis Group, 2022-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

1942-0862
1942-0870
10.1080/19420862.2021.2018960