論文 - 詳細
| RRC ID | 51879 |
|---|---|
| 著者 | Morishita M, Takahashi Y, Matsumoto A, Nishikawa M, Takakura Y. |
| タイトル | Exosome-based tumor antigens-adjuvant co-delivery utilizing genetically engineered tumor cell-derived exosomes with immunostimulatory CpG DNA. |
| ジャーナル | Biomaterials |
| Abstract |
For cancer immunotherapy via tumor antigen vaccination in combination with an adjuvant, major challenges include the identification of a particular tumor antigen and efficient delivery of the antigen as well as adjuvant to antigen-presenting cells. In this study, we proposed an efficient exosome-based tumor antigens-adjuvant co-delivery system using genetically engineered tumor cell-derived exosomes containing endogenous tumor antigens and immunostimulatory CpG DNA. Murine melanoma B16BL6 cells were transfected with a plasmid vector encoding a fusion streptavidin (SAV; a protein that binds to biotin with high affinity)-lactadherin (LA; an exosome-tropic protein) protein, yielding genetically engineered SAV-LA-expressing exosomes (SAV-exo). SAV-exo were combined with biotinylated CpG DNA to prepare CpG DNA-modified exosomes (CpG-SAV-exo). Fluorescent microscopic observation revealed the successful modification of exosomes with CpG DNA by SAV-biotin interaction. CpG-SAV-exo showed efficient and simultaneous delivery of exosomes with CpG DNA to murine dendritic DC2.4 cells in culture. Treatment with CpG-SAV-exo effectively activated DC2.4 cells and enhanced tumor antigen presentation capacity. Immunization with CpG-SAV-exo exhibited stronger in vivo antitumor effects in B16BL6 tumor-bearing mice than simple co-administration of exosomes and CpG DNA. Thus, genetically engineered CpG-SAV-exo is an effective exosome-based tumor antigens-adjuvant co-delivery system that will be useful for cancer immunotherapy. |
| 巻・号 | 111 |
| ページ | 55-65 |
| 公開日 | 2016-12-1 |
| DOI | 10.1016/j.biomaterials.2016.09.031 |
| PII | S0142-9612(16)30513-0 |
| PMID | 27723556 |
| MeSH | Adjuvants, Immunologic / administration & dosage* Adjuvants, Immunologic / genetics Animals Antigens, Neoplasm / administration & dosage* Antigens, Neoplasm / genetics Antigens, Neoplasm / immunology* Cell Line, Tumor CpG Islands / genetics DNA / genetics* Drug Combinations Exosomes / genetics Exosomes / immunology* Genetic Engineering / methods* Immunization / methods Immunotherapy / methods Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Nude Neoplasms, Experimental / genetics Neoplasms, Experimental / therapy* Treatment Outcome |
| IF | 10.317 |
| 引用数 | 77 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | B16/BL6(RCB2638) |