| RRC ID |
6511
|
| 著者 |
Motomura Y, Senju S, Nakatsura T, Matsuyoshi H, Hirata S, Monji M, Komori H, Fukuma D, Baba H, Nishimura Y.
|
| タイトル |
Embryonic stem cell-derived dendritic cells expressing glypican-3, a recently identified oncofetal antigen, induce protective immunity against highly metastatic mouse melanoma, B16-F10.
|
| ジャーナル |
Cancer Res
|
| Abstract |
We have recently established a method to generate dendritic cells from mouse embryonic stem cells. By introducing exogenous genes into embryonic stem cells and subsequently inducing differentiation to dendritic cells (ES-DC), we can now readily generate transfectant ES-DC expressing the transgenes. A previous study revealed that the transfer of genetically modified ES-DC expressing a model antigen, ovalbumin, protected the recipient mice from a challenge with an ovalbumin-expressing tumor. In the present study, we examined the capacity of ES-DC expressing mouse homologue of human glypican-3, a recently identified oncofetal antigen expressed in human melanoma and hepatocellular carcinoma, to elicit protective immunity against glypican-3-expressing mouse tumors. CTLs specific to multiple glypican-3 epitopes were primed by the in vivo transfer of glypican-3-transfectant ES-DC (ES-DC-GPC3). The transfer of ES-DC-GPC3 protected the recipient mice from subsequent challenge with B16-F10 melanoma, naturally expressing glypican-3, and with glypican-3-transfectant MCA205 sarcoma. The treatment with ES-DC-GPC3 was also highly effective against i.v. injected B16-F10. No harmful side effects, such as autoimmunity, were observed for these treatments. The depletion experiments and immunohistochemical analyses suggest that both CD8+ and CD4+ T cells contributed to the observed antitumor effect. In conclusion, the usefulness of glypican-3 as a target antigen for antimelanoma immunotherapy was thus shown in the mouse model using the ES-DC system. Human dendritic cells expressing glypican-3 would be a promising means for therapy of melanoma and hepatocellular carcinoma.
|
| 巻・号 |
66(4)
|
| ページ |
2414-22
|
| 公開日 |
2006-2-15
|
| DOI |
10.1158/0008-5472.CAN-05-2090
|
| PII |
66/4/2414
|
| PMID |
16489048
|
| MeSH |
Animals
Cell Differentiation / genetics
Cell Differentiation / immunology
Cell Line, Tumor
Dendritic Cells / cytology
Dendritic Cells / immunology*
Epitopes, T-Lymphocyte / immunology
Female
Glypicans
Heparan Sulfate Proteoglycans / biosynthesis
Heparan Sulfate Proteoglycans / genetics
Heparan Sulfate Proteoglycans / immunology*
Immunotherapy, Adoptive / methods*
Killer Cells, Natural / immunology
Male
Melanoma, Experimental / immunology*
Melanoma, Experimental / metabolism
Melanoma, Experimental / prevention & control
Melanoma, Experimental / therapy*
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
Stem Cells / cytology
Stem Cells / immunology*
T-Lymphocytes, Cytotoxic / immunology
|
| IF |
9.727
|
| 引用数 |
53
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
|
