Evaluation of cancer therapy with iPS-ML aiming at clinical development

• Project/Area Number: 26290057
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Kumamoto University
• Principal Investigator: SENJU Satoru 熊本大学, 大学院生命科学研究部(医), 准教授 (50274709)
• Co-Investigator(Kenkyū-buntansha): 植村 靖史 国立研究開発法人国立がん研究センター, その他部局等, その他 (40364781)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
• Keywords: がん治療 / 免疫療法 / 細胞治療 / iPS細胞 / 肝臓がん / インターフェロン / 免疫細胞療法 / 再生医療等製品 / がん / マクロファージ / 樹状細胞 / 胃がん / 膵臓がん / インーフェロン / 腹膜播種 / 肝転移 / 胃癌 / 膵臓癌

Outline of Final Research Achievements

We hypothesized that macrophages producing IFN-beta may be useful for anti-cancer therapy. However, it is impossible to amplify human peripheral blood monocytes and thus the quantity of macrophages generated by donated blood may be insufficient for clinical use. We established a method to induce proliferation of human iPS-cell derived myeloid cells (iPS-MC) by introduction of genes promoting cell proliferation to generate iPS-cell derived myeloid/macrophage cell line (iPS-ML).
When iPS-ML were injected into the mice with pre-established peritoneal tumors (xenograft model of peritoneally disseminated cancer), iPS-ML infiltrated into the tumor tissues. In xenograft models, iPS-ML introduced with an expression vector for IFN-beta (iPS-ML/IFN-beta) profoundly inhibited the growth of peritoneally disseminated human gastric and pancreatic cancer. In addition, therapy with iPS-ML/IFN-beta was effective in xenograft models of primary and metastatic liver cancer.

Research Products

• [Journal Article] Therapy of primary and metastatic liver cancer by human iPS cell-derived myeloid cells producing interferon-β. (2017)
  • Author(s): Sakisaka M, Haruta M, Komohara Y, Umemoto S, Matsumura K, Ikeda T, Takeya M, Inomata Y, Nishimura Y, Senju S.
  • Journal Title: J Hepato-Biliary-Pancreatic Sciences. Volume: - Issue: 2 Pages: 109-119
  • DOI: 10.1002/jhbp.422
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Generation of mouse pluripotent stem cell-derived proliferating myeloid cells as an unlimited source of functional antigen-presenting cells (2015)
  • Author(s): Zhang R, Liu T, Senju S, Haruta M, Hirosawa N, Suzuki M, Tatsumi M, Ueda N, Maki H, Nakatsuka R, Matsuoka Y, Sasaki Y, Tsuzuki S, Nakanishi H, Araki R, Abe M, Akatsuka Y, Sakamoto Y, Sonoda Y, Nishimura Y, Kuzushima K, Uemura Y
  • Journal Title: Cancer Immunol Res Volume: 印刷中 Issue: 6 Pages: 668-677
  • DOI: 10.1158/2326-6066.cir-14-0117
  • Peer Reviewed
• [Journal Article] Therapy of peritoneally disseminated colon cancer by TAP-deficient ES cell-derived macrophages in allogeneic recipients. (2014)
  • Author(s): Haga, E., Endo, Y., Haruta, M., Koba, C., Matsumura, K., Takamatsu, K., Ikeda, T., Nishimura, Y., and Senju, S.
  • Journal Title: The Journal of Immunology Volume: 193 Issue: 4 Pages: 2024-2033
  • DOI: 10.4049/jimmunol.1303473
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Degradation of amyloid beta by human induced pluripotent stem cell-derived macrophages expressing Neprilysin-2. (2014)
  • Author(s): Takamatsu, K., Ikeda, T., Haruta, M., Matsumura, K., Ogi, Y., Nakagata, N., Uchino, M., Ando, Y., Nishimura, Y., and Senju, S.
  • Journal Title: Stem Cell Research Volume: 13 Issue: 3 Pages: 442-453
  • DOI: 10.1016/j.scr.2014.10.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Application of iPS cell-derived macrophages to cancer therapy. (2014)
  • Author(s): Senju, S., Koba, C., Haruta, M., Matsunaga, Y., Matsumura, K., Haga, E., Sasaki, Y., Ikeda, T., Takamatsu, K., and Nishimura, Y.
  • Journal Title: OncoImmunology Volume: 14 Issue: 3 Pages: e27927-e27927
  • DOI: 10.4161/onci.27927
  • Peer Reviewed
• [Presentation] iPS細胞を用いたがんに対する免疫細胞治療 (2016)
  • Author(s): 千住 覚
  • Organizer: 日本再生医療学会
  • Place of Presentation: 大阪市
  • Year and Date: 2016-03-18
  • Invited
• [Presentation] iPS細胞由来のミエロイド細胞による胃がん腹膜播種治療法の開発 (2015)
  • Author(s): 千住 覚
  • Organizer: 千里ライフサイエンスセミナー
  • Place of Presentation: 大阪市
  • Year and Date: 2015-11-25
  • Invited
• [Presentation] iPS細胞を基盤とするがん免疫療法の実用化へ向けた取り組み (2015)
  • Author(s): 千住 覚
  • Organizer: 第30回日本生殖免疫学会
  • Place of Presentation: 熊本市
  • Year and Date: 2015-11-22
  • Invited
• [Presentation] Cancer therapy with iPS cell-derived myeloid cells (2015)
  • Author(s): 千住 覚
  • Organizer: 第77回日本血液学会
  • Place of Presentation: 金沢市
  • Year and Date: 2015-10-18
  • Invited
• [Presentation] Cancer therapy with ES cell-derived macrophages producing interferon in a mouse model (2015)
  • Author(s): Senju S, Haruta M, Mimori A, Matsumura K, Kanagawa K, Haga E, Imamura Y, Sakisaka M, Ikeda T, Nishimura Y
  • Organizer: 日本がん免疫学会
  • Place of Presentation: 東京都
  • Year and Date: 2015-07-09
  • Int'l Joint Research
• [Presentation] ゼノグラフとモデルにおける胃がん肝転移に対するiPS-MLによる治療の効果 (2014)
  • Author(s): 千住覚、匂坂正孝、春田美和、羽賀栄理子、松村桂子、今村悠哉、池田徳典、西村泰治
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Year and Date: 2014-09-26
• [Presentation] 細胞治療に向けた樹状細胞の可能性 (2014)
  • Author(s): 千住覚
  • Organizer: 第42回日本臨床免疫学会総会
  • Place of Presentation: 京王プラザホテル（東京都）
  • Year and Date: 2014-09-25
  • Invited
• [Presentation] iPS細胞を用いた癌に対する免疫細胞療法 (2014)
  • Author(s): 千住覚
  • Organizer: 遺伝子・デリバリー研究会第14回夏期セミナー
  • Place of Presentation: 阿蘇いこいの村（阿蘇市）
  • Year and Date: 2014-08-20
  • Invited
• [Presentation] iPS細胞由来のミエロイド細胞（iPS-ML）によるがん治療 (2014)
  • Author(s): 千住覚
  • Organizer: 第62回日本輸血・細胞治療学会総会
  • Place of Presentation: 奈良県文化会館（奈良市）
  • Year and Date: 2014-05-16
  • Invited