PD-L1 siRNA-hyaluronic acid conjugate for dual-targeted cancer immunotherapy
DC Field | Value | Language |
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dc.contributor.author | Kim, Suyeon | - |
dc.contributor.author | Heo, Roun | - |
dc.contributor.author | Song, Seok Ho | - |
dc.contributor.author | Song, Kwon-Ho | - |
dc.contributor.author | Shin, Jung Min | - |
dc.contributor.author | Oh, Se Jin | - |
dc.contributor.author | Lee, Hyo-Jung | - |
dc.contributor.author | Chung, Jo Eun | - |
dc.contributor.author | Park, Jae Hyung | - |
dc.contributor.author | Kim, Tae Woo | - |
dc.date.accessioned | 2022-08-13T11:40:17Z | - |
dc.date.available | 2022-08-13T11:40:17Z | - |
dc.date.created | 2022-08-12 | - |
dc.date.issued | 2022-06 | - |
dc.identifier.issn | 0168-3659 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/143024 | - |
dc.description.abstract | Foreignization " of tumor cells via delivery of a non-self foreign antigen (Ag) into tumors is an appealing strategy to initiate anti-tumor immunity that can facilitate tumor rejection by pre-existing foreign-Ag-reactive T cells. However, the immune-suppressive factors in the tumor microenvironment (TME) limit the durable and potent immune response of these cells against tumor antigens, stressing the need for improved tumor-foreignization strategies. Here, we demonstrate that blockade of programmed cell death ligand 1 (PD-L1) on both tumor cells and dendritic cells (DCs) can markedly potentiate the induction of tumor-reactive T cells, thereby strengthening the anti-tumor immunity ignited by tumor-foreignization. Specifically, we developed a polymeric nanoconjugate (PEG-HA-OVA/PPLs), consisting of siPD-L1-based polyplexes, PEGylated hyaluronic acid as the CD44-targeting moiety, and ovalbumin (OVA) as a model foreign antigen. Notably, PEG-HA-OVA/PPLs were simultaneously delivered into CD44high tumor cells and CD44high DCs, leading to efficient cross-presentation of OVA and downregulation of PD-L1 in both cell types. Importantly, the nanoconjugate not only allowed OVA specific T cells to vigorously reject the foreignized tumor cells but also reprogrammed the TME to elicit robust T-cell responses specific to the endogenous tumor Ags, eventually generating long-lasting protective immunity. Thus, our combination strategy represents an innovative approach for the induction of potent tumor immunity via a two-step consecutive immune boost against exogenous and endogenous tumor Ags. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER | - |
dc.subject | VACCINE POTENCY | - |
dc.subject | DENDRITIC CELLS | - |
dc.subject | TUMOR-CELLS | - |
dc.subject | T-CELLS | - |
dc.subject | EXPRESSION | - |
dc.subject | ANTIGEN | - |
dc.subject | EXPANSION | - |
dc.subject | DELIVERY | - |
dc.subject | IMMUNITY | - |
dc.title | PD-L1 siRNA-hyaluronic acid conjugate for dual-targeted cancer immunotherapy | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Tae Woo | - |
dc.identifier.doi | 10.1016/j.jconrel.2022.04.023 | - |
dc.identifier.scopusid | 2-s2.0-85129325690 | - |
dc.identifier.wosid | 000800261000001 | - |
dc.identifier.bibliographicCitation | JOURNAL OF CONTROLLED RELEASE, v.346, pp.226 - 239 | - |
dc.relation.isPartOf | JOURNAL OF CONTROLLED RELEASE | - |
dc.citation.title | JOURNAL OF CONTROLLED RELEASE | - |
dc.citation.volume | 346 | - |
dc.citation.startPage | 226 | - |
dc.citation.endPage | 239 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Multidisciplinary | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.subject.keywordPlus | VACCINE POTENCY | - |
dc.subject.keywordPlus | DENDRITIC CELLS | - |
dc.subject.keywordPlus | TUMOR-CELLS | - |
dc.subject.keywordPlus | T-CELLS | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | ANTIGEN | - |
dc.subject.keywordPlus | EXPANSION | - |
dc.subject.keywordPlus | DELIVERY | - |
dc.subject.keywordPlus | IMMUNITY | - |
dc.subject.keywordAuthor | Tumor foreignization | - |
dc.subject.keywordAuthor | Immune evasion | - |
dc.subject.keywordAuthor | Tumor microenvironment | - |
dc.subject.keywordAuthor | PD-L1 | - |
dc.subject.keywordAuthor | CD44 | - |
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