Dual anti-idiotypic purification of a novel, native-format biparatopic anti-MET antibody with improved in vitro and in vivo efficacy

Marie Godar, Virginia Morello, Ava Sadi, Anna Hultberg, Natalie De Jonge, Cristina Basilico, Valérie Hanssens, Michael Saunders, Bart N. Lambrecht, Mohamed El Khattabi, Hans De Haard, Paolo Michieli, Christophe Blanchetot

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Abstract

Bispecific antibodies are of great interest due to their ability to simultaneously bind and engage different antigens or epitopes. Nevertheless, it remains a challenge to assemble, produce and/or purify them. Here we present an innovative dual anti-idiotypic purification process, which provides pure bispecific antibodies with native immunoglobulin format. Using this approach, a biparatopic IgG1 antibody targeting two distinct, HGF-competing, non-overlapping epitopes on the extracellular region of the MET receptor, was purified with camelid single-domain antibody fragments that bind specifically to the correct heavy chain/light chain pairings of each arm. The purity and functionality of the anti-MET biparatopic antibody was then confirmed by mass spectrometry and binding experiments, demonstrating its ability to simultaneously target the two epitopes recognized by the parental monoclonal antibodies. The improved MET-inhibitory activity of the biparatopic antibody compared to the parental monoclonal antibodies, was finally corroborated in cell-based assays and more importantly in a tumor xenograft mouse model. In conclusion, this approach is fast and specific, broadly applicable and results in the isolation of a pure, novel and native-format anti-MET biparatopic antibody that shows superior biological activity over the parental monospecific antibodies both in vitro and in vivo.

Original languageEnglish
Article number31621
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Aug 22 2016

ASJC Scopus subject areas

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    Godar, M., Morello, V., Sadi, A., Hultberg, A., De Jonge, N., Basilico, C., Hanssens, V., Saunders, M., Lambrecht, B. N., El Khattabi, M., De Haard, H., Michieli, P., & Blanchetot, C. (2016). Dual anti-idiotypic purification of a novel, native-format biparatopic anti-MET antibody with improved in vitro and in vivo efficacy. Scientific Reports, 6, [31621]. https://doi.org/10.1038/srep31621