RT Journal Article
SR Electronic
T1 LegoBody: facile generation of bispecific and multi-specific antibodies
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2019.12.25.888586
DO 10.1101/2019.12.25.888586
A1 Shanshan Lang
A1 Su Yang
A1 Scott Bidlingmaier
A1 Nam-Kyung Lee
A1 Bin Liu
YR 2019
UL http://biorxiv.org/content/early/2019/12/27/2019.12.25.888586.abstract
AB Bispecific and multi-specific antibodies are capable of recognizing multiple ligands simultaneously or synergistically, creating complex biological interactions not achievable by monoclonal antibodies, thus expanding opportunities for novel therapy development. With the large number of monoclonal antibodies either approved or under clinical development, there are numerous opportunities to combine their specificities to further improve therapeutic potential. Although simple in concept, clinical development of bi- and multi-specific antibodies face several challenges, chief of which is how to efficiently and reliably produce bispecific and multi-specific antibodies with expected specificity and desired biophysical properties. In this study, we developed a modular approach that uses temporary linkers to enforce proper chain pairing and proteases such as thrombin to remove those linkers from the final product. Combined with the ‘knob-into-hole’ design, we can generate IgG-like, bi- or multi-specific antibodies from any pre-existing monoclonal antibodies. The approach is highly versatile and applicable to any monoclonal antibody pair or panel, expediting evaluation and therapeutic development of bi- and multi-specific antibodies.