Characterization of Receptor Binding Affinity for Vascular Endothelial Growth Factor with Interferometric Imaging Sensor

Biosensors (Basel). 2024 Jun 24;14(7):315. doi: 10.3390/bios14070315.

Abstract

Wet Age-related macular degeneration (AMD) is the leading cause of vision loss in industrialized nations, often resulting in blindness. Biologics, therapeutic agents derived from biological sources, have been effective in AMD, albeit at a high cost. Due to the high cost of AMD treatment, it is critical to determine the binding affinity of biologics to ensure their efficacy and make quantitative comparisons between different drugs. This study evaluates the in vitro VEGF binding affinity of two drugs used for treating wet AMD, monoclonal antibody-based bevacizumab and fusion protein-based aflibercept, performing quantitative binding measurements on an Interferometric Reflectance Imaging Sensor (IRIS) system. Both biologics can inhibit Vascular Endothelial Growth Factor (VEGF). For comparison, the therapeutic molecules were immobilized on to the same support in a microarray format, and their real-time binding interactions with recombinant human VEGF (rhVEGF) were measured using an IRIS. The results indicated that aflibercept exhibited a higher binding affinity to VEGF than bevacizumab, consistent with previous studies using ELISA and SPR. The IRIS system's innovative and cost-effective features, such as silicon-based semiconductor chips for enhanced signal detection and multiplexed analysis capability, offer new prospects in sensor technologies. These attributes make IRISs a promising tool for future applications in the development of therapeutic agents, specifically biologics.

Keywords: Age-related macular degeneration (AMD); Interferometric Reflectance Imaging Sensor (IRIS); Vascular Endothelial Growth Factor (VEGF); aflibercept; anti-VEGF drug; bevacizumab.

MeSH terms

  • Bevacizumab
  • Biosensing Techniques
  • Humans
  • Interferometry*
  • Macular Degeneration / metabolism
  • Protein Binding
  • Receptors, Vascular Endothelial Growth Factor
  • Recombinant Fusion Proteins
  • Vascular Endothelial Growth Factor A* / metabolism

Substances

  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Receptors, Vascular Endothelial Growth Factor
  • aflibercept
  • VEGFA protein, human
  • Recombinant Fusion Proteins

Grants and funding

This work was partially funded by the Boston University Ignition Program, by the National Science Foundation (NSF iCorps Award n2027109 and NSF-TT PFI Award n1941195).