Identification and optimization of peptide inhibitors to block VISTA/PSGL-1 interaction for cancer immunotherapy.
Acta Pharm Sin B
; 13(11): 4511-4522, 2023 Nov.
Article
in En
| MEDLINE
| ID: mdl-37969728
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:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Acta Pharm Sin B
Year:
2023
Document type:
Article
Affiliation country:
China