title: Reprogrammed chondrocytes engineered to produce IL-12 provide novel ex vivo immune-gene therapy for cancer.
abstract: The somatic cell reprogramming technology was applied to a novel and promising ex vivo immune-gene therapy strategy for cancer. To establish a novel ex vivo cytokine gene therapy of cancer using the somatic cell reprogramming procedures.
  
  
  
  Mouse fibroblasts were converted into chondrocytes and subsequently transduced with IL-12 gene. The resultant IL-12 induced chondrogenic cells were irradiated with x-ray and inoculated into mice bearing CT26 colon cancer.
  
  
  
  The irradiation at 20 Gy or higher totally eliminated the proliferative potential of the cells, while less significantly influencing the IL-12 production from the cells. An inoculation of the irradiated IL-12 induced chondrogenic cells significantly suppressed tumor by inducing tumor-specific cytotoxic T lymphocytes, enhancing natural killer tumoricidal activity and inhibiting tumor neoangiogenesis in the mice.
  
  
  
  The somatic cell reprogramming procedures may provide a novel and effective means to treat malignancies.
authors.affiliation: Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.|Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tada
authors.affiliation: Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Tsunao
authors.initials: T
authors.lastname: Kishida
authors.affiliation: Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Fujiwara
authors.affiliation: Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kosuga
authors.affiliation: Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Konishi
authors.affiliation: Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Komatsu
authors.affiliation: Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shiozaki
authors.affiliation: Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ichikawa
authors.affiliation: Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Eigo
authors.initials: E
authors.lastname: Otsuji
authors.affiliation: Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Osam
authors.initials: O
authors.lastname: Mazda
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D065150:Cellular Reprogramming; D019902:Chondrocytes / Q000502:physiology* / Q000637:transplantation; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy*; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000502:physiology*; D005818:Genetic Engineering; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D011839:Radiation, Ionizing; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D047368:Tumor Burden
chemical_list: D019496:Cancer Vaccines; D018664:Interleukin-12
keywords: IL-12; direct conversion; direct reprogramming; ex vivo gene therapy; immunotherapy; induced chondrogenic cell