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

PLoS One. 2020 Mar 5;15(3):e0229206. doi: 10.1371/journal.pone.0229206. eCollection 2020.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology*
  • Biosensing Techniques / methods*
  • China
  • Drug Development
  • Epitopes / immunology
  • European Union
  • High-Throughput Screening Assays
  • Humans
  • Programmed Cell Death 1 Receptor / chemistry
  • Programmed Cell Death 1 Receptor / immunology*
  • Protein Binding
  • Surface Plasmon Resonance
  • United States

Substances

  • Antibodies, Monoclonal
  • Epitopes
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor

Grants and funding

Amgen provided support for this study in the form of salary for PR. Adimab LLC also provided support for this study in the form of salaries for MEB, AL, MV, SD, IW-M, LZ, JHN, IB, IC, HL, MS, TS, JB and YX. Carterra also provided support in the form of salaries for DB and YNA. The funders also supported all the experiments and material presented in this manuscript. The funding organizations did not play any additional roles in the study design, data collection and analysis, decision to publish, or preparation of the manuscript with the exception that the legal departments and senior management of the respective funders did review and approve the manuscript for publication. The specific roles of these authors are articulated in the ‘author contributions’ section.