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  • Title: Blocking of the PD-1/PD-L1 interaction by a novel cyclic peptide inhibitor for cancer immunotherapy.
    Author: Zhai W, Zhou X, Zhai M, Li W, Ran Y, Sun Y, Du J, Zhao W, Xing L, Qi Y, Gao Y.
    Journal: Sci China Life Sci; 2021 Apr; 64(4):548-562. PubMed ID: 32737851.
    Abstract:
    The interaction of PD-1/PD-L1 allows tumor cells to escape from immune surveillance. Clinical success of the antibody drugs has proven that blockade of PD-1/PD-L1 pathway is a promising strategy for cancer immunotherapy. Here, we developed a cyclic peptide C8 by using Ph.D.-C7C phage display technology. C8 showed high binding affinity with hPD-1 and could effectively interfere the interaction of PD-1/PD-L1. Furthermore, C8 could stimulate CD8+ T cell activation in human peripheral blood mononuclear cells (PBMCs). We also observed that C8 could suppress tumor growth in CT26 and B16-OVA, as well as anti-PD-1 antibody resistant B16 mouse model. CD8 T cells infiltration significantly increased in tumor microenvironment, and IFN-γ secretion by CD8+ T cells in draining lymph nodes also increased. Simultaneously, we exploited T cells depletion models and confirmed that C8 exerted anti-tumor effects via activating CD8+ T cells dependent manner. The interaction model of C8 with hPD-1 was simulated and confirmed by alanine scanning. In conclusion, C8 shows anti-tumor capability by blockade of PD-1/PD-L1 interaction, and C8 may provide an alternative candidate for cancer immunotherapy.
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