RRC ID |
6500
|
著者 |
Matsuyoshi H, Senju S, Hirata S, Yoshitake Y, Uemura Y, Nishimura Y.
|
タイトル |
Enhanced priming of antigen-specific CTLs in vivo by embryonic stem cell-derived dendritic cells expressing chemokine along with antigenic protein: application to antitumor vaccination.
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ジャーナル |
J Immunol
|
Abstract |
Dendritic cell (DC)-based immunotherapy is regarded as a promising means for anti-cancer therapy. The efficiency of T cell-priming in vivo by transferred DCs should depend on their encounter with T cells. In the present study, we attempted to improve the capacity of DCs to prime T cells in vivo by genetic modification to express chemokine with a T cell-attracting property. For genetic modification of DCs, we used a recently established method to generate DCs from mouse embryonic stem cells. We generated double-transfectant DCs expressing a chemokine along with a model Ag (OVA) by sequential transfection of embryonic stem cells, and then induced differentiation to DCs. We comparatively evaluated the effect of three kinds of chemokines; secondary lymphoid tissue chemokine (SLC), monokine induced by IFN-gamma (Mig), and lymphotactin (Lptn). All three types of double transfectant DCs primed OVA-specific CTLs in vivo more efficiently than did DCs expressing only OVA, and the coexpression of SLC or Lptn was more effective than that of Mig. Immunization with DCs expressing OVA plus SLC or Mig provided protection from OVA-expressing tumor cells more potently than did immunization with OVA alone, and SLC was more effective than Mig. In contrast, coexpression of Lptn gave no additive effect on protection from the tumor. Collectively, among the three chemokines, expression of SLC was the most effective in enhancing antitumor immunity by transferred DCs in vivo. The findings provide useful information for the development of a potent DC-based cellular immunotherapy.
|
巻・号 |
172(2)
|
ページ |
776-86
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公開日 |
2004-1-15
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DOI |
10.4049/jimmunol.172.2.776
|
PMID |
14707047
|
MeSH |
Animals
CD4-Positive T-Lymphocytes / immunology
Cell Differentiation / genetics
Cell Differentiation / immunology
Cell Line
Cell Movement / genetics
Cell Movement / immunology
Cell Survival / immunology
Cells, Cultured
Chemokine CCL21
Chemokines / biosynthesis*
Chemokines / genetics
Chemokines, CC / administration & dosage
Chemokines, CC / biosynthesis
Chemokines, CC / physiology
Coculture Techniques
Dendritic Cells / cytology
Dendritic Cells / immunology*
Dendritic Cells / metabolism
Dendritic Cells / transplantation*
Egg Proteins / administration & dosage
Egg Proteins / biosynthesis*
Egg Proteins / immunology
Embryo, Mammalian
Epitopes, T-Lymphocyte / administration & dosage*
Epitopes, T-Lymphocyte / biosynthesis
Epitopes, T-Lymphocyte / immunology
Female
Gene Expression Profiling
Hybridomas
Immunotherapy, Active / methods
Injections, Intraperitoneal
Injections, Intravenous
Male
Melanoma, Experimental / immunology
Melanoma, Experimental / prevention & control*
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
Neoplasm Transplantation
Ovalbumin / administration & dosage
Ovalbumin / biosynthesis*
Ovalbumin / immunology
Peptide Fragments
Stem Cell Transplantation* / methods
T-Lymphocytes, Cytotoxic / immunology*
Transfection
|
IF |
4.886
|
引用数 |
51
|
WOS 分野
|
IMMUNOLOGY
|
リソース情報 |
ヒト・動物細胞 |
|