RRC ID 6511
Author Motomura Y, Senju S, Nakatsura T, Matsuyoshi H, Hirata S, Monji M, Komori H, Fukuma D, Baba H, Nishimura Y.
Title Embryonic stem cell-derived dendritic cells expressing glypican-3, a recently identified oncofetal antigen, induce protective immunity against highly metastatic mouse melanoma, B16-F10.
Journal 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.
Volume 66(4)
Pages 2414-22
Published 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
Times Cited 53
Human and Animal Cells