Identification and optimization of peptide inhibitors to block VISTA/PSGL-1 interaction for cancer immunotherapy

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.

Screening and identification of cell-penetrating peptides by display technology / 国际药学研究杂志

Screening and identification of cell-penetrating peptides(CPP)which have different functions by display technolo?gy are hot topics in recent years. Currently the most widely used display technology is phage display and mRNA display technology. This paper describes the principle and application of display technology such as phage display and mRNA display and reviews in detail the advance in study on the screening and identification of CPP by display technology in recent years.

Screening and identification of cell-penetrating peptides by display technology / 国际药学研究杂志

Screening and identification of cell-penetrating peptides, CPP which have different functions by display technology are hot topics in recent years. Currently the most widely used display technology is phage display and mRNA display technology. This paper describes the principle and application of display technology such as phage display and mRNA display and reviews in detail the advance in study on the screening and identification of CPP by display technology in recent years.

Screening the peptide high-binding VEGF receptor 3 with phage-displayed random peptide library / 第三军医大学学报

Objective To get a high affinity peptide of vascular endothelial growth factor receptor 3 (VEGFR3) as a potent carrier targeted to lymphangiogenesis of ovarian cancer via the technology of phage display. Methods Solid-phase was panned with direct VEGFR3 extracellular protein coating, then the unbound phage was washed away and the eluted phage was amplified. The positive phage clones were identified by ELISA and sequenced, and the affinity and specialty were identified by competent ELISA. Results After four-round bio-panning, the enriched positive phage clones were identified by ELISA. Eight positive phage clones were sequenced and 5 were consensus (WHGSLKQNLWWY). The short peptide displayed on screened positive phage could bind specifically to VEGFR3, and the binding could be inhibited by natural antibody VEGF-D. Conclusion The phage clone (phage-WHGSLKQNLWWY) obtained via bio-panning of peptide library has a high affinity with VEGF receptor 3. The peptide could be a potent carrier targeted to VEGFR3.