Details

Autor(en) / Beteiligte

• Brown, Michael E
• Bedinger, Daniel
• Lilov, Asparouh
• Rathanaswami, Palaniswami
• Vásquez, Maximiliano
• Durand, Stéphanie
• Wallace-Moyer, Ian
• Zhong, Lihui
• Nett, Juergen H
• Burnina, Irina
• Caffry, Isabelle
• Lynaugh, Heather
• Sinclair, Melanie
• Sun, Tingwan
• Bukowski, John
• Xu, Yingda
• Abdiche, Yasmina Noubia
• Mantis, Nicholas J.

Titel

Assessing the binding properties of the anti-PD-1 antibody landscape using label-free biosensors

Ist Teil von

• PloS one, 2020-03, Vol.15 (3), p.e0229206-e0229206

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2020

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Here we describe an industry-wide collaboration aimed at assessing the binding properties of a comprehensive panel of monoclonal antibodies (mAbs) against programmed cell death protein 1 (PD-1), an important checkpoint protein in cancer immunotherapy and validated therapeutic target, with well over thirty unique mAbs either in clinical development or market-approved in the United States, the European Union or China. The binding kinetics of the PD-1/mAb interactions were measured by surface plasmon resonance (SPR) using a Carterra LSA instrument and the results were compared to data collected on a Biacore 8K. The effect of chip type on the SPR-derived binding rate constants and affinities were explored and the results compared with solution affinities from Meso Scale Discovery (MSD) and Kinetic Exclusion Assay (KinExA) experiments. When using flat chip types, the LSA and 8K platforms yielded near-identical kinetic rate and affinity constants that matched solution phase values more closely than those produced on 3D-hydrogels. Of the anti-PD-1 mAbs tested, which included a portion of those known to be in clinical development or approved, the affinities spanned from single digit picomolar to nearly 425 nM, challenging the dynamic range of our methods. The LSA instrument was also used to perform epitope binning and ligand competition studies which revealed over ten unique competitive binding profiles within this group of mAbs.