Page 24 - D. Cancer biology

[D. Cancer biology-18]

Phage display-identified PD-L1-binding peptides reinvigorate

T-cell activity and inhibit tumor progression

Smriti Gurung¹˙²˙³, Minji Kim¹˙²˙³, Byungheon Lee¹˙²˙³˙*

¹Biochemistry & Cell Biology, School of Medicine, Kyungpook National University, Daegu 41944, South Korea,

²BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine,
Kyungpook National University, Daegu 41944, South Korea, ³CMRI , School of Medicine, Kyungpook National

University, Daegu 41944, South Korea

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-L1Pep-1 and PD-L1Pep-2 preferentially bound to high PD-L1-expressing cells over low PD-L1-

expressing cells; binding was further enhanced by interferon-γ, an inducer of PD-L1 expression. Binding affinities of
PD-L1Pep-1 and PD-L1Pep-2 were approximately 373 and 281 nM, respectively. The PD-L1-binding peptides

restored interferon-γ secretion and T-cell proliferation to cells inhibited by co-culture with tumor cells, dendritic
cells or culture on PD-L1-coated plates. Intravenously injected PD-L1Pep-1 and PD-L1Pep-2 efficiently homed to

tumor tissues, inhibited tumor growth, and increased CD8+/FoxP3+ ratio in mice. PD-L1-targeted liposomal
doxorubicin increased anti-tumor activity and CD8+/FoxP3+ ratio more than untargeted liposomal doxorubicin,

respectively. These results suggest that PD-L1Pep-1 and PD-L1Pep-2 block PD-L1 and reinvigorate T-cell activity,
inhibiting tumor growth by enhancing anti-tumor immunity