Novel anti-PD-L1 peptide selected from combinatorial phage library inhibits tumor cell growth and restores T-cell activity

Abstract

PD-L1 overexpression on tumour cells forms a protective shield against cytotoxic T-cell killing, which consequently leads to immune evasion. Engagement of PD-1 in tumour infiltrating T cells with PD-L1 results in an exhausted T-cell phenotype, thus preventing an effective immune response against tumour cells. In the present study, we employed phage display combinatorial peptide library to discover anti-PD-L1 peptides. The peptides discovered here, could computationally exhibit specific interactions with PD-L1 at residues with which PD-1 also interacts. Binding affinity and specificity of the peptides were examined by flow cytometry. Anti- tumour activity of peptides was also investigated using several cell-based assays. Surprisingly, we demonstrated that Pep-39 can inhibit PDL-1, and reduce MDA-MB-231, CT-26, and DU-145 cells survival. In co-culture experiments, Pep-39 restored proliferation of Jurkat cells cultured in the presence of MDA-MB-231 cells. In addition, Jurkat cells apoptosis was impeded, indicating blocking potential of Pep-39 against PD-1/PD-L1 interaction.