Identification and optimization of peptide inhibitors to block VISTA/PSGL-1 interaction for cancer immunotherapy
© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V..
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 promising candidates for cancer immunotherapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Acta pharmaceutica Sinica. B - 13(2023), 11 vom: 27. Nov., Seite 4511-4522 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Niu, Xiaoshuang [VerfasserIn] |
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| Links: |
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| Themen: |
Cancer immunotherapy |
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| Anmerkungen: |
Date Revised 12.02.2024 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.apsb.2023.08.003 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a 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 promising candidates for cancer immunotherapy | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Zhou, Xiuman |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Wenpeng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhai, Wenjie |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Aijun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Xiaowen |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Shengzhe |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Guanyu |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yanying |e verfasserin |4 aut | |
| 700 | 1 | |a Du, Jiangfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yahong |e verfasserin |4 aut | |
| 700 | 1 | |a Qiu, Lu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Wenshan |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Yanfeng |e verfasserin |4 aut | |
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