Engineering a High-Affinity PD-1 Peptide for Optimized Immune Cell-Mediated Tumor Therapy
Yilei Chen1, Hongxing Huang1, Yin Liu2
1Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China.
Cancer Research and Treatment
|August 6, 2021
Summary
A novel peptide, nABPD1, was computationally optimized to significantly enhance binding affinity to programmed cell death protein 1 (PD-1). This improved peptide effectively boosts cytokine-induced killer (ICIK) cell antitumor activity, offering a promising strategy against cancer immune escape.
Area of Science:
- Immunology
- Biotechnology
- Computational Biology
Background:
- Programmed cell death protein 1 (PD-1) is a key regulator of immune checkpoints, often exploited by cancer cells to evade immune surveillance.
- Peptides targeting the PD-1/PD-L1 pathway represent a potential therapeutic strategy to restore anti-tumor immunity.
Purpose of the Study:
- To computationally optimize a known PD-1 binding peptide (nABP284) to enhance its affinity for PD-1.
- To evaluate the efficacy of the optimized peptide in blocking PD-1 mediated immune suppression and enhancing anti-cancer activity.
Main Methods:
- Peptide optimization using AutoDock and PyMOL computational tools.
- Binding affinity assessment via Surface Plasmon Resonance (SPR).
- In vitro evaluation of anti-cancer activity using co-culture models with immune and cancer cells.
Main Results:
- The optimized peptide, nABPD1, exhibited a significantly higher binding affinity (KD=11.9 nM) compared to the original peptide nABP284 (KD=11.8 μM).
- nABPD1 demonstrated superior performance in enhancing interleukin-2 secretion from T cells and improving the in vitro anti-tumor efficacy of cytokine-induced killer (ICIK) cells.
Conclusions:
- The computationally designed peptide nABPD1 shows markedly increased affinity for PD-1.
- nABPD1 effectively blocks the PD-1/PD-L1 interaction, thereby enhancing ICIK cell-mediated anti-tumor immunity by 'armoring' ICIK cells.
