Identification and optimization of peptide inhibitors to block VISTA/PSGL-1 interaction for cancer immunotherapy
Acta Pharmaceutica Sinica B
;
(6): 4511-4522, 2023.
Article
in English
| WPRIM
| ID: wpr-1011181
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 promising candidates for cancer immunotherapy.
Full text:
Available
Index:
WPRIM (Western Pacific)
Language:
English
Journal:
Acta Pharmaceutica Sinica B
Year:
2023
Type:
Article
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