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Updated: Nov 7, 2025

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology
Published on: May 2, 2025
Specific intracellular binding peptide as sPD-L1 antibody mimic: Robust binding capacity and intracellular region
Junjie Hu1, Zhao-Huan Zhang2, Zhongzheng Zhu3
1Center for Molecular Recognition and Biosensing, School of Life Sciences, Shanghai University, Shanghai, 200444, PR China.
Abstract:
Programmed death ligand 1 (PD-L1) immune checkpoint has been regarded as a new target for predicting cancer immunotherapy. As a transmembrane protein, PD-L1 has very low blood concentration and is likely to deplete their native activity when separated from the membrane environment due to significant hydrophobic domains, which make it difficult to measure sensitively. The reported PD-L1 aptamers and antibodies are both extracellular region binding molecules with the overlapping binding sites, which seriously limit with the construction of biosensor. Specific intracellular binding peptide (SIBP) as a unique PD-L1 intracellular region homing probe molecule is utilized for specifically capture targets. A simple and sensitive surface plasmon resonance (SPR) sandwich assay was constructed to detect serum soluble PD-L1 (sPD-L1) based on the unique and strong binding ability of SIBP to the intracellular region of sPD-L1. The designed SPR sensor showed great selectivity and wide dynamic response range of sPD-L1 concentration from 10 ng/mL to 2000 ng/mL. The limit of detection was calculated to be 1.749 ng/mL (S/N = 3). Owing to the SIBP's strong and specific binding ability with sPD-L1, the sensitive sensor can successfully detect sPD-L1 in serum samples, paving the way for the development of efficient test tools for clinical diagnosis and analysis.
Insights
A novel biosensor effectively detects soluble Programmed death ligand 1 (sPD-L1) in serum. This surface plasmon resonance assay utilizes a unique peptide for sensitive and selective sPD-L1 measurement, aiding cancer immunotherapy prediction.
Area of Science:
- Biomedical Engineering
- Analytical Chemistry
- Immunology
Background:
- Programmed death ligand 1 (PD-L1) is a key target for cancer immunotherapy prediction.
- Measuring PD-L1 is challenging due to its low blood concentration and hydrophobic nature.
- Existing PD-L1 detection methods face limitations in biosensor construction due to overlapping binding sites.
Purpose of the Study:
- To develop a sensitive and selective biosensor for detecting serum soluble PD-L1 (sPD-L1).
- To overcome limitations of current PD-L1 detection methods.
- To enable efficient clinical diagnosis and analysis for cancer immunotherapy.
Main Methods:
- A surface plasmon resonance (SPR) sandwich assay was designed.
- A specific intracellular binding peptide (SIBP) was utilized as a probe for PD-L1.
- The assay was optimized for detecting sPD-L1 in serum samples.
Main Results:
- The SPR sensor demonstrated high selectivity for sPD-L1.
- A wide dynamic response range from 10 ng/mL to 2000 ng/mL was achieved.
- A low limit of detection of 1.749 ng/mL (S/N=3) was determined.
Conclusions:
- The SIBP-based SPR assay provides a sensitive and specific method for sPD-L1 detection.
- This biosensor shows potential for clinical diagnosis and monitoring of cancer immunotherapy.
- The developed tool paves the way for efficient cancer biomarker analysis.

