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

• DOI: 10.1371/journal.pone.0229206
• Publication Date: 2020-03-05T18:30:12Z
• Authors: Michael E. Brown; Daniel Bedinger; Asparouh Lilov; Palaniswami Ratha...; Maximiliano Vásquez; Stéphanie Durand; Ian Wallace-Moyer; Lihui Zhong; Juergen H. Nett; Irina Burnina; Isabelle Caffry; Heather Lynaugh; Melanie Sinclair; Tingwan Sun; John Bukowski; Yingda Xu; Yasmina Noubia Ab...
• Keywords: Receptor–ligand kinetics; Binding affinities; Affinities; Epitope mapping

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