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.
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.
Matsuyoshi
Hidetake
H
Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto 860-8556, Japan.
Senju
Satoru
S
Hirata
Shinya
S
Yoshitake
Yoshihiro
Y
Uemura
Yasushi
Y
Nishimura
Yasuharu
Y
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D054421:Chemokine CCL21; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D019742:Chemokines, CC / Q000008:administration & dosage / Q000096:biosynthesis / Q000502:physiology; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*; D004527:Egg Proteins / Q000008:administration & dosage / Q000096:biosynthesis* / Q000276:immunology; D004622:Embryo, Mammalian; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage* / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D006825:Hybridomas; D016233:Immunotherapy, Active / Q000379:methods; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009368:Neoplasm Transplantation; D010047:Ovalbumin / Q000008:administration & dosage / Q000096:biosynthesis* / Q000276:immunology; D010446:Peptide Fragments; D033581:Stem Cell Transplantation / Q000379:methods; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection
C515479:Ccl21c protein, mouse; D054421:Chemokine CCL21; D018925:Chemokines; D019742:Chemokines, CC; D004527:Egg Proteins; D018984:Epitopes, T-Lymphocyte; C110366:OVA-8; D010446:Peptide Fragments; D010047:Ovalbumin