title: [Cancer Immunotherapy Using Human Induced Pluripotent Stem Cell-Derived Dendritic Cells(iPSDCs)Expressing Carcinoembryonic Antigen].
abstract: The difficulty in obtaining a sufficient number of functional dendritic cells(DCs)is a well-known serious problem in DCbased immunotherapy. Therefore, we used induced pluripotent stem cell-derived DCs(iPSDCs). We have reported that mouse iPSDCs are equivalent to BMDCs, in terms of maturation and antigen presentation. In this study, the antitumor immune response of human iPSDCs expressing the carcinoembryonic antigen was examined, to determine its clinical application in gastrointestinal cancer. Human iPS cells were established from healthy human fibroblasts using a Sendai virus vector, and human iPSDCs were differentiated under a feeder-free culture. Additionally, the surface marker expression, cytokine production, and migratory capacity of human iPSDCs were equivalent to those of monocyte-derived DCs(MoDCs). After 3 cycles of stimulation of autologous PBMCs by genetically modified DCs, the 51Cr-release assay was performed. The lymphocytes stimulated by iPSDCs-CEA showed cytotoxic activity against LCL-CEA and CEA652-pulsed LCL, but showed no cytotoxicity against LCL-LacZ. In addition, they showed cytotoxic activity against CEA-positive human cancer cell lines, MKN45 and HT29, but showed no cytotoxicity against CEA-negative human cancer cell line MKN1. In conclusion, CEA-specific CTLs responses could be induced by iPSDCs-CEA. This vaccination strategy may be useful in future clinical applications of cancer vaccines.
authors.affiliation: Second Dept. of Surgery, Wakayama Medical University, School of Medicine.
authors.forename: Junya
authors.initials: J
authors.lastname: Kitadani
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Ojima
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Iwamoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tabata
authors.forename: Mikihito
authors.initials: M
authors.lastname: Nakamori
authors.forename: Masaki
authors.initials: M
authors.lastname: Nakamura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Katsuda
authors.forename: Motoki
authors.initials: M
authors.lastname: Miyazawa
authors.forename: Keiji
authors.initials: K
authors.lastname: Hayata
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamaue
mesh_terms: D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D057026:Induced Pluripotent Stem Cells / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy
chemical_list: D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen