Related Experiment Video
Updated: Mar 17, 2026
Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology
Published on: May 2, 2025
Magneto-nanosensor platform for probing low-affinity protein-protein interactions and identification of a
Jung-Rok Lee1, Daniel J B Bechstein1, Chin Chun Ooi2
1Department of Mechanical Engineering, Stanford University, Stanford, California 94305, USA.
Abstract:
Substantial efforts have been made to understand the interactions between immune checkpoint receptors and their ligands targeted in immunotherapies against cancer. To carefully characterize the complete network of interactions involved and the binding affinities between their extracellular domains, an improved kinetic assay is needed to overcome limitations with surface plasmon resonance (SPR). Here, we present a magneto-nanosensor platform integrated with a microfluidic chip that allows measurement of dissociation constants in the micromolar-range. High-density conjugation of magnetic nanoparticles with prey proteins allows multivalent receptor interactions with sensor-immobilized bait proteins, more closely mimicking natural-receptor clustering on cells. The platform has advantages over traditional SPR in terms of insensitivity of signal responses to pH and salinity, less consumption of proteins and better sensitivities. Using this platform, we characterized the binding affinities of the PD-1-PD-L1/PD-L2 co-inhibitory receptor system, and discovered an unexpected interaction between the two known PD-1 ligands, PD-L1 and PD-L2.
Insights
A new magneto-nanosensor platform enables precise measurement of immune checkpoint interactions. This technology revealed a novel binding interaction between PD-L1 and PD-L2, crucial for cancer immunotherapy research.
Area of Science:
- Biotechnology and Biomedical Engineering
- Immunology and Cancer Research
Background:
- Understanding immune checkpoint receptor-ligand interactions is vital for cancer immunotherapy.
- Existing methods like surface plasmon resonance (SPR) have limitations in characterizing these interactions.
Purpose of the Study:
- To develop an improved kinetic assay for characterizing immune checkpoint interactions and binding affinities.
- To overcome the limitations of traditional SPR assays for studying extracellular domain interactions.
Main Methods:
- Development of a magneto-nanosensor platform integrated with a microfluidic chip.
- High-density conjugation of magnetic nanoparticles with prey proteins for multivalent receptor interactions.
- Measurement of dissociation constants (Kd) in the micromolar range.
Main Results:
- The magneto-nanosensor platform demonstrated advantages over SPR, including insensitivity to pH/salinity, reduced protein consumption, and enhanced sensitivity.
- Characterization of the binding affinities within the PD-1/PD-L1/PD-L2 co-inhibitory receptor system.
- Discovery of an unexpected interaction between PD-L1 and PD-L2.
Conclusions:
- The developed magneto-nanosensor platform offers a sensitive and robust method for studying immune checkpoint interactions.
- The identified PD-L1 and PD-L2 interaction provides new insights into immune regulation and potential therapeutic targets in cancer.
More Related Videos
10:18Author Spotlight: Magnetic Fluorescent Bead-Based Dual-Reporter Flow Analysis of PDL1-Vaxx Peptide Vaccine-Induced Antibody Blockade of the PD-1/PD-L1 Interaction
Published on: July 7, 2023
08:10A Liquid Phase Affinity Capture Assay Using Magnetic Beads to Study Protein-Protein Interaction: The Poliovirus-Nanobody Example
Published on: May 29, 2012