Therapeutic effect of human iPS-cell-derived myeloid cells expressing IFN-β against peritoneally disseminated cancer in xenograft models

• Published in: PloS one Vol. 8; no. 6; p. e67567
• Main Authors: Koba, Chihiro, Haruta, Miwa, Matsunaga, Yusuke, Matsumura, Keiko, Haga, Eriko, Sasaki, Yuko, Ikeda, Tokunori, Takamatsu, Koutaro, Nishimura, Yasuharu, Senju, Satoru
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.06.2013; Public Library of Science (PLoS)
• Subjects: Animal models; Animal tissues; Animals; Antigens; Biology; Cancer; Cancer therapies; Cell growth; Cell Line, Tumor; Cell Proliferation; Cytokines - pharmacology; Dendritic cells; Gastric cancer; Humans; Induced Pluripotent Stem Cells - cytology; Injections, Intraperitoneal; Interferon; Interferon-beta - metabolism; Kinases; Macrophage colony-stimulating factor; Macrophages; Macrophages - pathology; Medicine; Mice; Mice, SCID; Myeloid cells; Myeloid Cells - metabolism; Myeloid Cells - transplantation; Pancreatic cancer; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - therapy; Peritoneal Neoplasms - secondary; Peritoneal Neoplasms - therapy; Peritoneum; Peritoneum - metabolism; Peritoneum - pathology; Receptor, ErbB-2 - metabolism; Science; Senescence; Single-Chain Antibodies - metabolism; Stem Cell Transplantation; Stem cells; Stomach cancer; Studies; Tumors; Xenograft Model Antitumor Assays; Xenografts; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0067567

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.