Anti-CTLA-4 antibody-functionalized dendritic cell-derived exosomes targeting tumor-draining lymph nodes for effective induction of antitumor T-cell responses
DC Field | Value | Language |
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dc.contributor.author | Cao Dai Phung | - |
dc.contributor.author | Thanh Tung Pham | - |
dc.contributor.author | Hanh Thuy Nguyen | - |
dc.contributor.author | Tien Tiep Nguyen | - |
dc.contributor.author | Ou, Wenquan | - |
dc.contributor.author | Jeong, Jee-Heon | - |
dc.contributor.author | Choi, Han-Gon | - |
dc.contributor.author | Ku, Sae Kwang | - |
dc.contributor.author | Yong, Chul Soon | - |
dc.contributor.author | Kim, Jong Oh | - |
dc.date.accessioned | 2021-06-22T05:59:11Z | - |
dc.date.available | 2021-06-22T05:59:11Z | - |
dc.date.created | 2021-01-21 | - |
dc.date.issued | 2020-10 | - |
dc.identifier.issn | 1742-7061 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/826 | - |
dc.description.abstract | The therapeutic efficacy of current cancer vaccines is far from optimal, mainly because of insufficient induction of antigen-specific T cells and because tumor cells can hijack immunosuppressive mechanisms to evade the immune responses. Generating specific, robust, and long-term immune responses against cancer cells and the attenuating of immunosuppressive factors are critical for effective cancer vaccination. Recently, the engineering of exosomes specifically bind to T cells, and then stimulating tumor-specific T-cell immune responses has emerged as a potential alternative strategy for cancer vaccination. In this study, we generated a bifunctional exosome combining the strategy of vaccination and checkpoint blockade. Exosomes prepared from Ovalbumin (OVA)-pulsed, activated dendritic cells were modified with anti-CTLA-4 antibody (EXO-OVA-mAb) to block this inhibitory molecule and to enhance the specificity of the exosomes toward T cells. Our study provides a unique strategy for functionalizing exosome membrane with anti-CTLA-4 antibody via lipid-anchoring method to synergize efficacy of cancer vaccination and immune checkpoint blockade against the tumor. Statement of Significance We designed T-cell-targeting exosomes (EXO-OVA-mAb) decorated with costimulatory molecules, MHCs, antigenic OVA peptide, and anti-CTLA-4 antibody, combining the strategies of vaccines and checkpoint blockade. The exosomes showed enhanced binding to T cells in tumor-draining lymph nodes, effectively induced T-cell activation, and improved the tumor homing of effector T cells, ultimately significantly restraining tumor growth. Thus, EXO-OVA-mAb greatly facilitates T-cell targeting, induces a strong tumorspecific T-cell response, and increased the ratio of effector T cells/regulatory T cells within tumors, resulting in appreciable tumor growth inhibition. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER SCI LTD | - |
dc.title | Anti-CTLA-4 antibody-functionalized dendritic cell-derived exosomes targeting tumor-draining lymph nodes for effective induction of antitumor T-cell responses | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Choi, Han-Gon | - |
dc.identifier.doi | 10.1016/j.actbio.2020.08.008 | - |
dc.identifier.scopusid | 2-s2.0-85089733394 | - |
dc.identifier.wosid | 000577511200028 | - |
dc.identifier.bibliographicCitation | ACTA BIOMATERIALIA, v.115, pp.371 - 382 | - |
dc.relation.isPartOf | ACTA BIOMATERIALIA | - |
dc.citation.title | ACTA BIOMATERIALIA | - |
dc.citation.volume | 115 | - |
dc.citation.startPage | 371 | - |
dc.citation.endPage | 382 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Engineering | - |
dc.relation.journalResearchArea | Materials Science | - |
dc.relation.journalWebOfScienceCategory | Engineering, Biomedical | - |
dc.relation.journalWebOfScienceCategory | Materials Science, Biomaterials | - |
dc.subject.keywordPlus | REGULATORY T | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | CTLA-4 | - |
dc.subject.keywordPlus | DELIVERY | - |
dc.subject.keywordPlus | NANOPARTICLES | - |
dc.subject.keywordPlus | INHIBITION | - |
dc.subject.keywordPlus | PACLITAXEL | - |
dc.subject.keywordPlus | BLOCKADE | - |
dc.subject.keywordPlus | ACTIVATE | - |
dc.subject.keywordPlus | VACCINES | - |
dc.subject.keywordAuthor | Exosome | - |
dc.subject.keywordAuthor | Lymph node | - |
dc.subject.keywordAuthor | T cell | - |
dc.subject.keywordAuthor | Cancer vaccines | - |
dc.subject.keywordAuthor | CTLA-4 checkpoint | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S1742706120304682?via%3Dihub | - |
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