Immunotherapy against Metastatic Melanoma with Human iPS Cell-Derived Myeloid Cell Lines Producing Type I Interferons

• Project/Area Number: 15K19694
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Kumamoto University
• Principal Investigator: Miyashita Azusa 熊本大学, 医学部附属病院, 病院教員 (20467989)
• Research Collaborator: SENJU Satoru
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 癌免疫療法 / 悪性黒色腫 / iPS細胞 / 進行期悪性黒色腫 / 新規免疫細胞療法

Outline of Final Research Achievements

The purpose of this study is to develop new immune cell therapy using iPS cells for malignant melanoma. We focused on macrophages for immune cell therapy because the macrophage infiltration is frequently observed in solids cancers. We have decided to use iPS cell-derived macropage which genetically modified to express type I IFNs for treatment against melanoma. We call them iPS cell-derived myeloid cell lines expressing type I IFNs (iPS-ML-IFNs).
In this study, we examined the efficacy of human iPS-ML-IFNs against human melanoma cells. The iPS-ML-IFNs exhibited significant effects in inhibiting the growth of the tumors against the disseminated human melanoma cells in SCID mice. On the other hand, treatment with iPS-ML without IFNs demonstrated no inhibitory effect on cancer cell growth.
We believe this method will provide a new therapeutic modality for metastatic melanoma.

Research Products

• [Journal Article] Immunotherapy against Metastatic Melanoma with Human iPS Cell-Derived Myeloid Cell Lines Producing Type I Interferons. (2016)
  • Author(s): Miyashita A, Fukushima S, Nakahara S, Kubo Y, Tokuzumi A, Yamashita J, Aoi J, Haruta M, Senju S, Nishimura Y, Jinnin M, Ihn H
  • Journal Title: Cancer Immunol Res Volume: 3 Issue: 3 Pages: 248-258
  • DOI: 10.1158/2326-6066.cir-15-0096
  • Peer Reviewed / Open Access
• [Journal Article] Investigation of FOXM1 as a Potential New Target for Melanoma. (2015)
  • Author(s): Miyashita A, Fukushima S, Nakahara S, Yamashita J, Tokuzumi A, Aoi J, Ichihara A, Kanemaru H, Jinnin M, Ihn H.
  • Journal Title: PLoS One. Volume: 10 Issue: 12 Pages: e0144241-e0144241
  • DOI: 10.1371/journal.pone.0144241
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Immunotherapy against Metastatic Melanoma with Human iPS Cell-Derived Myeloid Cell Lines Producing Type I Interferons. (2015)
  • Author(s): Miyashita A, Fukushima S, Nakahara S, Kubo Y, Tokuzumi A, Yamashita J, Aoi J, Haruta M, Senju S, Nishimura Y, Jinnin M, Ihn H.
  • Journal Title: Cancer Immunol Res. Volume: 4 Pages: 248-58
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Hair shaft miRNA-221 levels as a new tumor marker of malignant melanoma (2015)
  • Author(s): Inada T, Fukushima S, Murai M, Jinnin M, Miyashita A, Nakahara S, Yamashita J, Aoi J, Masuguchi S, Ihn H.
  • Journal Title: J Dermatol. Volume: 42 Issue: 2 Pages: 198-201
  • DOI: 10.1111/1346-8138.12730
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Serum long non-coding RNA, snoRNA host gene 5 level as a new tumor marker of malignant melanoma. (2015)
  • Author(s): Ichigozaki Y, Fukushima S, Jinnin M, Miyashita A, Nakahara S, Tokuzumi A, Yamashita J, Kajihara I, Aoi J, Masuguchi S, Zhongzhi W, Ihn H.
  • Journal Title: Exp Dermatol. Volume: 25 Issue: 1 Pages: 67-69
  • DOI: 10.1111/exd.12868
  • Peer Reviewed / Open Access
• [Presentation] 1.Immunotherapy with human iPS cell-derived myeloid cell lines producing type I interferons against metastatic melanoma (2016)
  • Author(s): Miyashita Azusa
  • Organizer: the 16th World Congress on Cancers of the skin
  • Place of Presentation: ウィーン
  • Year and Date: 2016-08-31
  • Int'l Joint Research
• [Presentation] 遺伝子改変ヒトiPS細胞由来マクロファージ様細胞を用いた進行期悪性黒色腫の免疫療法 (2015)
  • Author(s): 宮下 梓、福島 聡、中原智史、徳澄亜紀、久保洋介、千住 覚、西村泰治、神人正寿、尹 浩信
  • Organizer: 第43回日本臨床免疫学会
  • Place of Presentation: 神戸国際会議場(神戸)
  • Year and Date: 2015-10-22
• [Presentation] 強皮症におけるcobble stone appearanceの臨床的意義 (2015)
  • Author(s): 福島 聡、梶原一亨、宮下 梓、神人正寿、尹 浩信
  • Organizer: 第43回日本臨床免疫学会
  • Place of Presentation: 神戸国際会議場(神戸)
  • Year and Date: 2015-10-22
• [Presentation] Immunotherapy with human iPS-cell derived myeloid cell lines producing type I interferons against metastatic melanoma. (2015)
  • Author(s): Miyashita A, Fukushima S, Senju S, Nishimura Y, Jinnin M, Ihn H.
  • Organizer: International Conference of Cancer Immunology and Macrophages
  • Place of Presentation: 東京大学 伊藤国際学術センター内 伊藤謝恩ホール(東京)
  • Year and Date: 2015-07-09
  • Int'l Joint Research
• [Presentation] 鼻尖・鼻背部の皮膚欠損に対しWheatly法による再建を行った2例 (2015)
  • Author(s): 宮下 梓、福島 聡、野田知香、澤村創一郎、梶原一亨、青井 淳、市原麻子、増口信一、神人正寿、尹 浩信
  • Organizer: 第31回日本皮膚悪性腫瘍学会
  • Place of Presentation: 大阪国際会議場（大阪）
  • Year and Date: 2015-07-03
• [Presentation] 慢性型頸部放線菌症の1例 (2015)
  • Author(s): 緒方聡子、宮下 梓、新森大祐、神人正寿、尹 浩信、矢口貴志
  • Organizer: 第114回日本皮膚科学会総会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2015-05-29