Reference - Detail
| RRC ID | 37621 |
|---|---|
| Author | Fujii S, Goto A, Shimizu K. |
| Title | Antigen mRNA-transfected, allogeneic fibroblasts loaded with NKT-cell ligand confer antitumor immunity. |
| Journal | Blood |
| Abstract |
The maturation of dendritic cells (DCs) in situ by danger signals plays a central role in linking innate and adaptive immunity. We previously demonstrated that the activation of invariant natural killer T (iNKT) cells by administration of alpha-galactosylceramide (alpha-GalCer)-loaded tumor cells can act as a cellular adjuvant through the DC maturation. In the current study, we used allogeneic fibroblasts loaded with alpha-GalCer and transfected with antigen-encoding mRNA, thus combining the adjuvant effects of iNKT-cell activation with delivery of antigen to DCs in vivo. We found that these cells produce antigen protein and activate NK and iNKT cells. When injected into major histocompatibility complex (MHC)-mismatched mice, they elicited antigen-specific T-cell responses and provided tumor protection, suggesting that these immune responses depend on host DCs. In addition, antigen-expressing fibroblasts loaded with alpha-GalCer lead to a more potent T-cell response than those expressing NK cell ligands. Thus, glycolipid-loaded, mRNA-transfected allogeneic fibroblasts act as cellular vectors to provide iNKT-cell activation, leading to DC maturation and T-cell immunity. By harnessing the innate immune system and generating an adaptive immune response to a variety of antigens, this unique tool could prove clinically beneficial in the development of immunotherapies against malignant and infectious diseases. |
| Volume | 113(18) |
| Pages | 4262-72 |
| Published | 2009-4-30 |
| DOI | 10.1182/blood-2008-08-176446 |
| PII | S0006-4971(20)39236-3 |
| PMID | 19164596 |
| MeSH | Animals Antigens, CD1d / immunology Antigens, CD1d / metabolism Antigens, Neoplasm / genetics* Dendritic Cells / immunology Dendritic Cells / metabolism Female Fibroblasts / immunology* Galactosylceramides / metabolism Green Fluorescent Proteins / genetics Green Fluorescent Proteins / metabolism Histocompatibility Antigens Class I / metabolism Humans Immunity Immunity, Cellular Intramolecular Oxidoreductases / administration & dosage Intramolecular Oxidoreductases / genetics Intramolecular Oxidoreductases / metabolism Killer Cells, Natural / immunology* Male Melanoma, Experimental / immunology Melanoma, Experimental / prevention & control* Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic NIH 3T3 Cells RNA, Messenger / genetics* Reverse Transcriptase Polymerase Chain Reaction T-Lymphocytes / immunology* Transfection Vaccination |
| IF | 17.794 |
| Times Cited | 27 |
| WOS Category | HEMATOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 3 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | NIH3T3 |