Journal Article

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

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

2020

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Affinity / Antibodies / Antigenic determinants / Apoptosis / Binding / Biochemistry / Biology and Life Sciences / Biosensors / Cancer immunotherapy / Cancer treatment / Cell death / Cemiplimab / Comparative analysis / Detection equipment / Engineering and Technology / Epitopes / Health aspects / Hydrogels / Immunoglobulins / Immunotherapy / Kinetics / Ligands / Measurement techniques / Medical equipment / Methods / Monoclonal antibodies / Nivolumab / PD-1 protein / Pembrolizumab / Phase matching / Physical Sciences / Proteins / Rate constants / Research and Analysis Methods / Sensors / Surface plasmon resonance / Surface science / Therapeutic applications