| 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
|
| リソース情報 |
| ヒト・動物細胞 |
B16/BL6(RCB2638) |
