RRC ID |
58078
|
著者 |
Matsumoto A, Takahashi Y, Ariizumi R, Nishikawa M, Takakura Y.
|
タイトル |
Development of DNA-anchored assembly of small extracellular vesicle for efficient antigen delivery to antigen presenting cells.
|
ジャーナル |
Biomaterials
|
Abstract |
Tumor-cell derived small extracellular vesicle (sEV) combined with immunostimulatory adjuvants may serve as a promising tumor vaccine through the induction of the cytotoxic T cell response. To achieve an efficient immune response, the prolonged tissue residence after intradermal injection followed by the sustained and efficient delivery of tumor-cell derived sEV combined with adjuvants to antigen-presenting cells (APCs) is a promising strategy. In the present study, we constructed a DNA-anchored sEV superstructure in which tumor-cell derived sEVs were assembled with each other to achieve prolonged tissue residence and the ability to encourage selective uptake by dendritic cells. We prepared sEVs modified with immunostimulatory CpG-DNA containing an additional "sticky end" (CpG-sEV). CpG-sEVs were mixed with an oligonucleotide duplex containing the sequence complementary to the "sticky end" of the CpG-DNA, resulting in the self-assembly of CpG-sEV into a micrometer-sized superstructure. The CpG-DNA anchored sEV assembly (CpG-sEV assembly) was selectively taken up by APCs, compared to tumor cells or fibroblast cells, and it efficiently activated dendritic cells in vitro. Moreover, CpG-sEV assembly formation significantly prolonged tissue residence and increased the immune responses of immunostimulatory CpG-DNA intradermally injected into mice. These results indicate that CpG-sEV assembly is an effective system which may be useful for tumor immunotherapy.
|
巻・号 |
225
|
ページ |
119518
|
公開日 |
2019-12-1
|
DOI |
10.1016/j.biomaterials.2019.119518
|
PII |
S0142-9612(19)30617-9
|
PMID |
31586864
|
MeSH |
Animals
Antigen-Presenting Cells / metabolism*
Antigens / administration & dosage*
Cytokines / metabolism
DNA / metabolism*
Endocytosis / drug effects
Extracellular Vesicles / metabolism*
Immunomodulation / drug effects
Injections, Intradermal
Male
Melanoma, Experimental / immunology
Melanoma, Experimental / pathology
Mice, Inbred C57BL
Oligodeoxyribonucleotides / pharmacology
|
IF |
10.317
|
引用数 |
3
|
リソース情報 |
ヒト・動物細胞 |
B16/BL6(RCB2638) |