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Updated: Jan 3, 2026
Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology
Published on: May 2, 2025
In vitro assay for the development of small molecule inhibitors targeting PD-1/PD-L1
Wenjie Zhai1, Xiuman Zhou2, Jiangfeng Du1
1School of Life Sciences, Zhengzhou University, Zhengzhou, China.
Abstract:
Cancer immunotherapy has recently emerged as one of the hot research field since clinical successes achieved by antibody drugs of immune checkpoints, among which PD-1 and its ligand PD-L1 are the well established molecules. PD-1/PD-L1 pathway induces immune tolerance and immune evasion, especially in tumor microenvironment, cancer cell is capable to escape the immune surveillance by up-regulating the expression level of PD-1 or PD-L1. Blockade of PD-1/PD-L1 can unleash the anti-tumor activity, and the strategy shows great successes in the treatment of various cancer types in the late stage. Beside antibody drugs, many other molecules such as peptides, high affinity PD(L)-1 mutants, chemical compounds, and DNA aptamers are designed for inhibitors of PD-1/PD-L1 pathway. Each modulators show their pros and cons based on their own physiochemical properties. Here we introduced the methods for identifying low molecular weight inhibitors of PD-1/PD-L1 and mainly discussed the cell-based blocking test.
Insights
Researchers explored methods to identify small molecule inhibitors targeting the PD-1/PD-L1 pathway, a key mechanism in cancer immune evasion. Cell-based blocking assays were central to this investigation for developing novel cancer immunotherapies.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Cancer immunotherapy has advanced significantly due to immune checkpoint inhibitors, particularly targeting the PD-1/PD-L1 pathway.
- The PD-1/PD-L1 pathway promotes immune tolerance and evasion within the tumor microenvironment, allowing cancer cells to escape immune surveillance.
- Blocking the PD-1/PD-L1 interaction can restore anti-tumor immunity and has shown success in treating various advanced cancers.
Purpose of the Study:
- To introduce methods for identifying low molecular weight inhibitors of the PD-1/PD-L1 pathway.
- To discuss the application of cell-based blocking tests in the discovery of novel PD-1/PD-L1 inhibitors.
Main Methods:
- Development and application of cell-based blocking assays to screen for inhibitors.
- Evaluation of various small molecule modulators, including peptides, PD(L)-1 mutants, chemical compounds, and DNA aptamers.
Main Results:
- Established cell-based assays are effective for identifying and characterizing low molecular weight inhibitors of PD-1/PD-L1.
- Different classes of inhibitors exhibit unique physiochemical properties, influencing their efficacy and application.
Conclusions:
- Cell-based blocking tests are crucial for discovering novel, low molecular weight inhibitors of the PD-1/PD-L1 pathway.
- These findings contribute to the development of alternative strategies beyond antibody-based therapies for cancer immunotherapy.
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