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

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dc.contributor.authorGurung, Smritiko
dc.contributor.authorKhan, Fatimako
dc.contributor.authorGunassekaran, Gowri Rangaswamyko
dc.contributor.authorDo Yoo, Jaeko
dc.contributor.authorVadevoo, Sri Murugan Poongkavithaiko
dc.contributor.authorPermpoon, Uttapolko
dc.contributor.authorKim, Sang-Hyunko
dc.contributor.authorKim, Ha-Jeongko
dc.contributor.authorKim, In-Sanko
dc.contributor.authorHan, Hyeonjeongko
dc.contributor.authorPark, Ji-Hoko
dc.contributor.authorKim, Soyounko
dc.contributor.authorLee, Byungheonko
dc.date.accessioned2020-05-07T07:20:06Z-
dc.date.available2020-05-07T07:20:06Z-
dc.date.created2020-05-06-
dc.date.created2020-05-06-
dc.date.issued2020-07-
dc.identifier.citationBIOMATERIALS, v.247-
dc.identifier.issn0142-9612-
dc.identifier.urihttp://hdl.handle.net/10203/274136-
dc.description.abstractBlockade 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.-
dc.languageEnglish-
dc.publisherELSEVIER SCI LTD-
dc.titlePhage display-identified PD-L1-binding peptides reinvigorate T-cell activity and inhibit tumor progression-
dc.typeArticle-
dc.identifier.wosid000526972100004-
dc.identifier.scopusid2-s2.0-85082805236-
dc.type.rimsART-
dc.citation.volume247-
dc.citation.publicationnameBIOMATERIALS-
dc.identifier.doi10.1016/j.biomaterials.2020.119984-
dc.contributor.localauthorPark, Ji-Ho-
dc.contributor.nonIdAuthorGurung, Smriti-
dc.contributor.nonIdAuthorKhan, Fatima-
dc.contributor.nonIdAuthorGunassekaran, Gowri Rangaswamy-
dc.contributor.nonIdAuthorDo Yoo, Jae-
dc.contributor.nonIdAuthorVadevoo, Sri Murugan Poongkavithai-
dc.contributor.nonIdAuthorPermpoon, Uttapol-
dc.contributor.nonIdAuthorKim, Sang-Hyun-
dc.contributor.nonIdAuthorKim, Ha-Jeong-
dc.contributor.nonIdAuthorKim, In-San-
dc.contributor.nonIdAuthorKim, Soyoun-
dc.contributor.nonIdAuthorLee, Byungheon-
dc.description.isOpenAccessN-
dc.type.journalArticleArticle-
dc.subject.keywordAuthorImmune checkpoint blockade-
dc.subject.keywordAuthorPD-1-
dc.subject.keywordAuthorPD-L1-
dc.subject.keywordAuthorPeptides-
dc.subject.keywordAuthorPhage display-
dc.subject.keywordAuthorT-cell activity-
dc.subject.keywordPlusPD-1/PD-L1 INTERACTION-
dc.subject.keywordPlusANTI-PD-L1 ANTIBODY-
dc.subject.keywordPlusDEATH 1-
dc.subject.keywordPlusCANCER-
dc.subject.keywordPlusPD-1-
dc.subject.keywordPlusEXPRESSION-
dc.subject.keywordPlusBLOCKADE-
dc.subject.keywordPlusBLOCKING-
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