title: Therapy of primary and metastatic liver cancer by human iPS cell-derived myeloid cells producing interferon-β.
abstract: BACKGROUND
  iPS-ML are myeloid lineage cells with a proliferative capacity derived from induced pluripotent stem (iPS) cells. This study aimed to examine therapeutic effect of iPS-ML producing interferon-β (iPS-ML/IFN-β) towards primary and metastatic liver cancer and investigate the mechanism of that effect.
  
  
  METHODS
  We established a xenograft model of liver metastasis by injecting the spleen of SCID mice with MKN-45 human gastric cancer cells and also a primary liver cancer model by injecting SK-HEP-1 human hepatocellular carcinoma cells into the liver. After cancer lesions were established, iPS-ML/IFN-β was administered by intraperitoneal injection, and therapeutic effect was evaluated.
  
  
  RESULTS
  The i.p. injection of iPS-ML/IFN-β resulted in a significant retardation of cancer progression and prolonged mouse survival. The infiltration of i.p. administered iPS-ML into tumor lesions located below the liver capsule was observed, suggesting tumor-directed migration and penetration of the liver capsule by iPS-ML. The IFN-β concentration in the liver was maintained at levels sufficient to exert an anti-cancer effect for at least 3 days post-injection, accounting for the potent therapeutic effect obtained by injection two to three times per week.
  
  
  CONCLUSIONS
  This study demonstrates the therapeutic potential of the iPS-ML/IFN-β in patients with liver cancer.
authors.affiliation: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.|Department of Transplantation and Pediatric Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Sakisaka
authors.affiliation: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
authors.forename: Miwa
authors.initials: M
authors.lastname: Haruta
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komohara
authors.affiliation: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Umemoto
authors.affiliation: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Matsumura
authors.affiliation: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
authors.forename: Tokunori
authors.initials: T
authors.lastname: Ikeda
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
authors.affiliation: Department of Transplantation and Pediatric Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Inomata
authors.affiliation: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Nishimura
authors.affiliation: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Senju
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000556:secondary / Q000628:therapy*; D064987:Cell- and Tissue-Based Therapy; D004195:Disease Models, Animal; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation*; D016899:Interferon-beta / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000556:secondary / Q000628:therapy*; D016513:Mice, SCID; D022423:Myeloid Cells / Q000637:transplantation*; D013274:Stomach Neoplasms / Q000473:pathology / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D016899:Interferon-beta
keywords: Carcinoma; Hepatocellular; Immunotherapy; Interferon; Liver neoplasms