摘要
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.-C7 C phage display technology.C8 showed high binding affinity with h PD-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-γsecretion 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 h PD-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.
基金
supported by the National Natural Science Foundation of China(81822043,U1604286)
Key Scientific Research Projects of Henan Higher Education Institutions(18A180033,16A180037)
the Key Incubation Fund of SYSU(19ykzd29)。
