Phage display-identified PD-L1-binding peptides reinvigorate T-cell activity and inhibit tumor progression

Cited 0 time in webofscience Cited 0 time in scopus
  • Hit : 66
  • Download : 0
Blockade of programmed cell death ligand-1 (PD-L1) restores T-cell activity and enhances anti-tumor immunity. Screening a phage-displayed peptide library for peptides that selectively bind to PD-L1-overexpressing cells identified two peptides, CLQKTPKQC and CVRARTR (PD-L1Pep-1 and PD-L1Pep-2, respectively) that appeared to block PD-L1. PD-L1 Pep-1 and PD-L1 Pep-2 preferentially bound to high PD-L1 -expressing cells over low PD-L1-expressing cells; binding was further enhanced by interferon-gamma, an inducer of PD-L1 expression. Binding affinities of PD-L1 Pep-1 and PD-L1 Pep-2 were approximately 373 and 281 nM, respectively. Cellular binding of the PD-L1-binding peptides was reduced by silencing PD-Ll gene expression or competition with anti-PD-Ll antibody. PD-L1 Pep-1 and PD-L1 Pep-2 induced the internalization and downregulated cell surface levels of PD-Ll. The PD-L1-binding peptides restored cytokine secretion and T-cell proliferation to cells inhibited by co-culture with tumor cells or culture on PD-L1-coated plates. Intravenously injected PD-L1 Pep-1 and PD-L1 Pep-2 efficiently homed to tumor tissues, inhibited tumor growth, and increased CD8 + /FoxP3 + ratio in mice. The PD-Ll -binding peptides in combination with doxorubicin or PD-Ll -targeted liposomal doxorubicin inhibited tumor growth and increased CD8 + /FoxP3 + ratio more efficiently than doxorubicin alone and untargeted liposomal doxorubicin, respectively. These results suggest that PD-L1Pep-1 and PD-L1 Pep-2 block PD-Ll and reinvigorate T-cell activity, inhibiting tumor growth by enhancing anti-tumor immunity.
Publisher
ELSEVIER SCI LTD
Issue Date
2020-07
Language
English
Article Type
Article
Citation

BIOMATERIALS, v.247

ISSN
0142-9612
DOI
10.1016/j.biomaterials.2020.119984
URI
http://hdl.handle.net/10203/274136
Appears in Collection
BiS-Journal Papers(저널논문)
Files in This Item
There are no files associated with this item.

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0