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- W4385652556 abstract "Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8+ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by D-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8+ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as a promising candidate for cancer immunotherapy." @default.
- W4385652556 created "2023-08-09" @default.
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- W4385652556 date "2023-08-01" @default.
- W4385652556 modified "2023-10-17" @default.
- W4385652556 title "Identification and optimization of peptide inhibitors to block VISTA/PSGL-1 interaction for cancer immunotherapy" @default.
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- W4385652556 doi "https://doi.org/10.1016/j.apsb.2023.08.003" @default.
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