Anti-CTLA-4 antibody-functionalized dendritic cell-derived exosomes targeting tumor-draining lymph nodes for effective induction of antitumor T-cell responses
- Authors
- Cao Dai Phung; Thanh Tung Pham; Hanh Thuy Nguyen; Tien Tiep Nguyen; Ou, Wenquan; Jeong, Jee-Heon; Choi, Han-Gon; Ku, Sae Kwang; Yong, Chul Soon; Kim, Jong Oh
- Issue Date
- Oct-2020
- Publisher
- ELSEVIER SCI LTD
- Keywords
- Exosome; Lymph node; T cell; Cancer vaccines; CTLA-4 checkpoint
- Citation
- ACTA BIOMATERIALIA, v.115, pp.371 - 382
- Indexed
- SCIE
SCOPUS
- Journal Title
- ACTA BIOMATERIALIA
- Volume
- 115
- Start Page
- 371
- End Page
- 382
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/826
- DOI
- 10.1016/j.actbio.2020.08.008
- ISSN
- 1742-7061
- 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.
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