Engineering a High-Affinity PD-1 Peptide for Optimized Immune Cell-Mediated Tumor Therapy

Purpose The purpose of this study was to optimize a peptide (nABP284) that binds programmed cell death protein 1 (PD-1) by computer-based protocol in order increase its affinity. Then, aimed determine the inhibitory effects on cancer immune escape coculturing improving cytokine-induced killer (ICIK) cells with cells. Materials and Methods nABP284 PD-1 identified phage display technology our previous study. AutoDock PyMOL were used sequence design new (nABPD1). Immunofluorescence demonstrate peptides bound PD-1. Surface plasmon resonance measure binding affinity peptides. blocking effect evaluated neutralization experiment human recombinant death-ligand (PD-L1) protein. inhibition activated lymphocytes simulated acute T lymphocytic leukemia (Jurkat cells) tongue squamous carcinoma (Cal27 cells). anticancer activities determined ICIK Cal27 vitro. Results A high-affinity (nABPD1, KD=11.9 nM) for obtained optimizing (KD=11.8 μM). nABPD1 showed better efficacy than terms increasing secretion interkeulin-2 Jurkat enhancing vitro antitumor activity Conclusion possesses higher nABP284, which significantly enhances ability block PD-1/PD-L1 interaction cell-mediated armoring Key words: PD-1, Peptide optimization, Affinity, Computer simulation, Immune checkpoint inhibitor, Improving cells, Immunotherapy