Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 김광명 | * |
dc.date.accessioned | 2022-11-03T16:31:01Z | - |
dc.date.available | 2022-11-03T16:31:01Z | - |
dc.date.issued | 2022 | * |
dc.identifier.issn | 0142-9612 | * |
dc.identifier.issn | 1878-5905 | * |
dc.identifier.other | OAK-32496 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/262851 | - |
dc.description.abstract | Immune checkpoint blockade (ICB) has shown remarkable therapeutic efficacy in a variety of cancers. However, patients exhibit unexpectedly low response rates to ICB therapy owing to the unwanted recycling and cellular abundance of PD-L1. Herein, rational design of PD-L1 multivalent binding liposome is investigated through PEGylated liposomes incorporating different ratios of PD-L1 binding peptide. Liposomes incorporating 10 mol% PD-L1 binding peptides (10-PD-L1-Lipo) promote the multivalent binding with PD-L1 on tumor cell surface, which is endocytosed for its trafficking toward the lysosomes instead of the recycling endosomes. Thereby, 10PD-L1-Lipo leads to a significant PD-L1 degradation that prevents its recycling and cellular abundance compared to anti-PD-L1 antibody, disrupting immune escape mechanism of tumor cells and enhancing T cell-mediated antitumor immunity. Moreover, a clinically applicable doxorubicin (DOX) liposomal formulation is established via drug encapsulation into 10-PD-L1-Lipo. The resulting DOX-PD-L1-Lipo primes tumors via immunogenic chemotherapy by preferential DOX accumulation by the EPR effect and overcomes PD-L1 abundance induced following chemotherapy through multivalent binding-mediated PD-L1 degradation. As a result, the synergistic immunogenic chemotherapy and multivalent binding-mediated PD-L1 degradation by DOX-PD-L1-Lipo show significantly enhanced antitumor efficacy and immune responses in colon tumor models. Collectively, this study suggests the rationally designed PEGylated liposomes to promote PD-L1 multivalent binding providing a new route for safe and more effective ICB therapy. | * |
dc.language | English | * |
dc.publisher | ELSEVIER SCI LTD | * |
dc.subject | Cancer immunotherapy | * |
dc.subject | Immune checkpoint blockade | * |
dc.subject | PEGylated liposome | * |
dc.subject | Multivalent binding | * |
dc.subject | PD-L1 binding peptide | * |
dc.title | Liposome-mediated PD-L1 multivalent binding promotes the lysosomal degradation of PD-L1 for T cell-mediated antitumor immunity | * |
dc.type | Article | * |
dc.relation.volume | 290 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.journaltitle | BIOMATERIALS | * |
dc.identifier.doi | 10.1016/j.biomaterials.2022.121841 | * |
dc.identifier.wosid | WOS:000876551100001 | * |
dc.identifier.scopusid | 2-s2.0-85139240012 | * |
dc.author.google | Yang, Suah | * |
dc.author.google | Shim, Man Kyu | * |
dc.author.google | Song, Sukyung | * |
dc.author.google | Cho, Hanhee | * |
dc.author.google | Choi, Jiwoong | * |
dc.author.google | Jeon, Seong Ik | * |
dc.author.google | Kim, Woo Jun | * |
dc.author.google | Um, Wooram | * |
dc.author.google | Park, Jae Hyung | * |
dc.author.google | Yoon, Hong Yeol | * |
dc.author.google | Kim, Kwangmeyung | * |
dc.contributor.scopusid | 김광명(34770853900) | * |
dc.date.modifydate | 20240318112445 | * |