| RRC ID |
66034
|
| 著者 |
Morishita M, Takahashi Y, Nishikawa M, Ariizumi R, Takakura Y.
|
| タイトル |
Enhanced Class I Tumor Antigen Presentation via Cytosolic Delivery of Exosomal Cargos by Tumor-Cell-Derived Exosomes Displaying a pH-Sensitive Fusogenic Peptide.
|
| ジャーナル |
Mol Pharm
|
| Abstract |
Tumor-cell-derived exosomes contain endogenous tumor antigens and can be used as a potential cancer vaccine without requiring identification of the tumor-specific antigen. To elicit an effective antitumor effect, efficient tumor antigen presentation by MHC class I molecules on dendritic cells (DC) is desirable. Because DC endocytose exosomes, an endosomal escape mechanism is required for efficient MHC class I presentation of exosomal tumor antigens. In the present study, efficient cytosolic delivery of exosomal tumor antigens was performed using genetically engineered tumor-cell-derived exosomes and pH-sensitive fusogenic GALA peptide. Murine melanoma B16BL6 cells were transfected with a plasmid vector encoding a streptavidin (SAV; a protein that binds to biotin with high affinity)-lactadherin (LA; an exosome-tropic protein) fusion protein to obtain SAV-LA-modified exosomes (SAV-exo). SAV-exo was mixed with biotinylated GALA to obtain GALA-modified exosomes (GALA-exo). Fluorescent microscopic observation using fluorescent-labeled GALA showed that the exosomes were modified with GALA. GALA-exo exerted a membrane-lytic activity under acidic conditions and efficiently delivered exosomal cargos to the cytosol. Moreover, DC treated with GALA-exo showed enhanced tumor antigen presentation capacity by MHC class I molecules. Thus, genetically engineered GALA-exo are effective in controlling the intracellular traffic of tumor-cell-derived exosomes and for enhancing tumor antigen presentation capacity.
|
| 巻・号 |
14(11)
|
| ページ |
4079-4086
|
| 公開日 |
2017-11-6
|
| DOI |
10.1021/acs.molpharmaceut.7b00760
|
| PMID |
28977747
|
| MeSH |
Antigen Presentation / immunology
Antigens, Neoplasm / immunology
Antigens, Neoplasm / metabolism
Cytosol / metabolism
Dendritic Cells / immunology
Dendritic Cells / metabolism
Exosomes / chemistry*
Humans
Hydrogen-Ion Concentration
Peptides / chemistry*
Peptides / immunology*
|
| IF |
4.321
|
| リソース情報 |
| ヒト・動物細胞 |
B16/BL6(RCB2638) |
