Immunogenic Extracellular Vesicles Derived from Endoplasmic Reticulum-Stressed Tumor Cells: Implications as the Therapeutic Cancer Vaccine

Tumor-derived extracellular vesicles (TDEs) have potential for therapeutic cancer vaccine applications since they innately possess tumor-associated antigens, mediate antigen presentation, and can incorporate immune adjuvants for enhanced vaccine efficacy. However, the original TDEs also contain immu...

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Bibliographic Details
Published in:ACS nano 2024-01, Vol.18 (1), p.199-209
Main Authors: Han, Kyung Hee, Kim, Chan Ho, Kim, So Hee, Lee, Chang Hyun, Park, Minsung, Bui, Van Dat, Duong, Van Hieu, Kwon, Seunglee, Ha, Minji, Kang, Heegun, Park, Jae Hyung
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic
Animals
Cancer Vaccines - therapeutic use
Dendritic Cells
Endoplasmic Reticulum
Extracellular Vesicles
Mice
Neoplasms - therapy
T-Lymphocytes, Cytotoxic
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Summary:Tumor-derived extracellular vesicles (TDEs) have potential for therapeutic cancer vaccine applications since they innately possess tumor-associated antigens, mediate antigen presentation, and can incorporate immune adjuvants for enhanced vaccine efficacy. However, the original TDEs also contain immune-suppressive proteins. To address this, we proposed a simple yet powerful preconditioning method to improve the overall immunogenicity of the TDEs. This approach involved inducing endoplasmic reticulum (ER) stress on parental tumor cells via N-glycosylation inhibition with tunicamycin. The generated immunogenic TDEs (iTDEs) contained down-regulated immunosuppressive proteins and up-regulated immune adjuvants, effectively activating dendritic cells (DCs) in vitro. Furthermore, in vivo evidence from a tumor-bearing mouse model showed that iTDEs activated DCs, enabling cytotoxic T lymphocytes (CTLs) to target tumors, and eventually established a systemic antitumor immune response. Additionally, iTDEs significantly delayed tumor recurrence in a postsurgery model compared with control groups. These findings highlight the immense potential of our strategy for utilizing TDEs to develop effective cancer vaccines.
ISSN:1936-0851
1936-086X
DOI:10.1021/acsnano.3c05645