Whispering Gallery Modes-based biosensors for real-time monitoring and binding characterization of antibody-based cancer immunotherapeutics

Jimena Alvarez Freile, Ghizlane Choukrani, Kerstin Zimmermann, Edwin Bremer*, Lars Daehne

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Development of novel protein-based drugs such as antibodies or immunocytokines and initial validation of target binding typically occurs in 2D settings with e.g., surface plasmon resonance or reflection interferometry using antigen-coated planar sensors. However, a versatile tool to assess binding characteristics of tumour-targeting therapeutics where specific biochemical interactions can be monitored in real-time and in a more realistic 3D interaction setting is currently lacking. Here, we report on the development of versatile small optical 3D biosensors using protein G-coated spherical microparticles based on Whispering Gallery Modes (WGMs). These sensors allowed for an oriented immobilization of theoretically any immunoglobulin G (IgG) and IgG crystallizable fragment domain (Fc)-tagged protein and have been carefully optimized for specific detection of antigenantibody interactions, as illustrated using the Epithelial Growth Factor Receptor (EGFR) antibody Cetuximab and Program Death Ligand 1 (PD-L1) antibody Atezolizumab. When both ligand and analyte contained an Fcfragment, protein G binding capacity saturation followed by a "blocking" step with an irrelevant IgG enabled the label-free detection of Fc-tagged antigens with corresponding cognate ligands, as identified using EGFR-Fc, PD-L1-Fc and different members from the tumour necrosis factor receptor family, such as CD27-Fc and 4- 1BBFc. Thus, WGMs and developed protein G-coated biosensors provide a widely applicable tool to evaluate binding of immunotherapeutics to their targets on the sensor surface, imitating cell surface properties.

Original languageEnglish
Article number130512
Number of pages9
JournalSensors and actuators b-Chemical
Publication statusPublished - 1-Nov-2021


  • Whispering Gallery Modes
  • Optical biosensor
  • Cancer immunotherapy
  • Drug development
  • Label-free analytics

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