title: Therapeutic effect of human iPS-cell-derived myeloid cells expressing IFN-β against peritoneally disseminated cancer in xenograft models.
abstract: We recently developed a method to generate myeloid cells with proliferation capacity from human iPS cells. iPS-ML (iPS-cell-derived myeloid/macrophage line), generated by introducing proliferation and anti-senescence factors into iPS-cell-derived myeloid cells, grew continuously in an M-CSF-dependent manner. A large number of cells exhibiting macrophage-like properties can be readily obtained by using this technology. In the current study, we evaluated the possible application of iPS-ML in anti-cancer therapy. We established a model of peritoneally disseminated gastric cancer by intraperitoneally injecting NUGC-4 human gastric cancer cells into SCID mice. When iPS-ML were injected intraperitoneally into the mice with pre-established peritoneal NUGC-4 tumors, iPS-ML massively accumulated and infiltrated into the tumor tissues. iPS-ML expressing IFN-β (iPS-ML/IFN-β) significantly inhibited the intra-peritoneal growth of NUGC-4 cancer. Furthermore, iPS-ML/IFN-β also inhibited the growth of human pancreatic cancer MIAPaCa-2 in a similar model. iPS-ML are therefore a promising treatment agent for peritoneally disseminated cancers, for which no standard treatment is currently available.
authors.affiliation: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Koba
authors.forename: Miwa
authors.initials: M
authors.lastname: Haruta
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Matsunaga
authors.forename: Keiko
authors.initials: K
authors.lastname: Matsumura
authors.forename: Eriko
authors.initials: E
authors.lastname: Haga
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Tokunori
authors.initials: T
authors.lastname: Ikeda
authors.forename: Koutaro
authors.initials: K
authors.lastname: Takamatsu
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Satoru
authors.initials: S
authors.lastname: Senju
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016207:Cytokines / Q000494:pharmacology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D007274:Injections, Intraperitoneal; D016899:Interferon-beta / Q000378:metabolism*; D008264:Macrophages / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D022423:Myeloid Cells / Q000378:metabolism* / Q000637:transplantation*; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy; D010534:Peritoneal Neoplasms / Q000556:secondary / Q000628:therapy*; D010537:Peritoneum / Q000378:metabolism / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D057127:Single-Chain Antibodies / Q000378:metabolism; D033581:Stem Cell Transplantation; D023041:Xenograft Model Antitumor Assays
chemical_list: D016207:Cytokines; D016899:Interferon-beta; D018719:Erb-b2 Receptor Tyrosine Kinases; D057127:Single-Chain Antibodies; C508053:ERBB2 protein, human