RRC ID 6500
Author Matsuyoshi H, Senju S, Hirata S, Yoshitake Y, Uemura Y, Nishimura Y.
Title 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.
Journal 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.
Volume 172(2)
Pages 776-86
Published 2004-1-15
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
Times Cited 51
Human and Animal Cells