Reference - Detail
| RRC ID | 66034 |
|---|---|
| Author | Morishita M, Takahashi Y, Nishikawa M, Ariizumi R, Takakura Y. |
| Title | Enhanced Class I Tumor Antigen Presentation via Cytosolic Delivery of Exosomal Cargos by Tumor-Cell-Derived Exosomes Displaying a pH-Sensitive Fusogenic Peptide. |
| Journal | 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. |
| Volume | 14(11) |
| Pages | 4079-4086 |
| Published | 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 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 5 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | B16/BL6(RCB2638) |