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)