Related Experiment Video
Updated: Feb 17, 2026
Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology
Published on: May 2, 2025
Peptide Blocking of PD-1/PD-L1 Interaction for Cancer Immunotherapy
Chunlin Li1,2, Nengpan Zhang1, Jundong Zhou3
1CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, China.
Abstract:
Immunotherapy has become a promising alternative therapeutic approach for cancer patients. Interruption of immune checkpoints, such as CTLA-4 and PD-1, has been verified to be a successful means for cancer therapy in clinical trials. mAb targeting PD-L1 has been approved to treat urothelial carcinoma, non-small cell lung cancer, or Merkel cell carcinoma by the FDA. However, the high cost of the antibody can limit its application. In our study, targeting PD-L1 peptide (TPP-1), which specifically binds to PD-L1 with high affinity, was identified through bacterial surface display methods. Using a T-cell activation assay and mixed lymphocyte reaction, TPP-1 was verified to interfere with the interaction of PD-1/PD-L1. To examine the inhibitory effect of TPP-1 on tumor growth in vivo, a xenograft mouse model using H460 cells was established. The growth rate of tumor masses in TPP-1 or PD-L1 antibody-treated mice was 56% or 71% lower than that in control peptide-treated mice, respectively, indicating that TPP-1 inhibits, or at least retards, tumor growth. IHC of the tumors showed that IFNγ and granzyme B expression increased in the TPP-1 or PD-L1 antibody-treated groups, indicating that TPP-1 attenuates the inhibitory effect of PD-L1 on T cells and that T cells may get reactivated. On the basis of our data, TPP-1 peptide could work as an alternative to antibodies for tumor immunotherapy. Cancer Immunol Res; 6(2); 178-88. ©2017 AACR.
Insights
A novel peptide, TPP-1, targeting PD-L1, effectively inhibits tumor growth by interfering with PD-1/PD-L1 interactions. This peptide shows potential as a cost-effective alternative to antibody immunotherapy for cancer treatment.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Immunotherapy, particularly targeting immune checkpoints like PD-1/PD-L1, is a key cancer treatment strategy.
- Monoclonal antibodies (mAbs) targeting PD-L1 are FDA-approved but costly.
- There is a need for more accessible immunotherapeutic agents.
Purpose of the Study:
- To identify and characterize a peptide targeting PD-L1 (TPP-1) as a potential alternative to antibody therapy.
- To evaluate the efficacy of TPP-1 in inhibiting tumor growth and reactivating T cells.
Main Methods:
- Bacterial surface display was used to identify TPP-1, a peptide with high affinity for PD-L1.
- In vitro assays (T-cell activation, mixed lymphocyte reaction) assessed TPP-1's interference with PD-1/PD-L1 interaction.
- A xenograft mouse model (H460 cells) was used to evaluate TPP-1's in vivo anti-tumor effects.
Main Results:
- TPP-1 demonstrated high-affinity binding to PD-L1 and interfered with PD-1/PD-L1 interaction.
- In vivo, TPP-1 treatment reduced tumor growth by 56% compared to control.
- Immunohistochemistry revealed increased IFNγ and granzyme B expression, indicating T-cell reactivation.
Conclusions:
- TPP-1 peptide effectively inhibits tumor growth and reactivates T cells.
- TPP-1 represents a promising, potentially more affordable, alternative to PD-L1 antibodies for cancer immunotherapy.
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