Generation of large number of dendritic cells by induction of monocyte amplification

• Project/Area Number: 25640091
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• 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, 准教授 (50274709)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 樹状細胞 / 単球 / がん治療 / ワクチン / 細胞治療 / 免疫療法 / がん / 細胞培養 / 細胞分化 / 細胞増殖 / がん抗原

Outline of Final Research Achievements

We developed a method to expand human monocytes through lentivirus-mediated introduction of cMYC and BMI1, and we named the monocyte-derived proliferating cells, CD14-ML. CD14-ML differentiated into functional DC (CD14-ML-DC) upon addition of IL-4, resulting in the generation of a large number of DC. One drawback of this method was the extensive donor-dependent variation in proliferation efficiency. In the current study, we found that introduction of BCL2 or LYL1 along with cMYC and BMI1 was beneficial. Using the improved method, we obtained CD14-ML from all samples, regardless of whether the donors were healthy individuals or cancer patients. This improved method enables the generation of a sufficient number of DC for vaccination therapy from a small amount of peripheral blood from cancer patients. Information on T cell epitopes is not necessary in vaccination with cancer antigen-expressing CD14-ML-DC.

Research Products

• [Journal Article] Generation of Large Numbers of Antigen-Expressing Human Dendritic Cells Using CD14-ML Technology (2016)
  • Author(s): Yuya Imamura, Miwa Haruta, Yusuke Tomita, Keiko Matsumura, Tokunori Ikeda, Akira Yuno1, Masatoshi Hirayama, Hideki Nakayama, Hiroshi Mizuta, Yasuharu Nishimura, Satoru Senju
  • Journal Title: Plos One Volume: 11 Issue: 4 Pages: e0152384-e0152384
  • DOI: 10.1371/journal.pone.0152384
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Generation of a large number of functional dendritic cells from human monocytes expanded by forced expression of cMYC plus BMI1. (2013)
  • Author(s): Haruta, M., Tomita, Y., Imamura, Y., Matsumura, K., Ikeda, T., Takamatsu, K., Nishimura,Y., and Senju, S.
  • Journal Title: Human Immunol Volume: 74 Issue: 10 Pages: 1400-1408
  • DOI: 10.1016/j.humimm.2013.05.017
  • Peer Reviewed
• [Presentation] ヒト末梢血単球の増殖誘導法、および、これを用いた樹状細胞の大量産生技術の開発 (2015)
  • Author(s): Yuya Imamura, Miwa Haruta, Yusuke Tomita, Keiko Matsumura, Tokunori Ikeda, Akira Yuno, Masahiko Hirayama, Yasuharu Nishimura, Satoru Senju
  • Organizer: 日本樹状細胞研究会
  • Place of Presentation: 岡山市
  • Year and Date: 2015-07-10
• [Presentation] Cancer antigen-expressing CD14ML-derived DC as a potential means for vaccination therapy (2015)
  • Author(s): Yuya Imamura, Miwa Haruta, Yusuke Tomita, Keiko Matsumura, Tokunori Ikeda, Akira Yuno, Masahiko Hirayama, Yasuharu Nishimura, Satoru Senju
  • Organizer: 日本がん免疫学会
  • Place of Presentation: 東京都
  • Year and Date: 2015-07-09
• [Presentation] ヒトの末梢決単球の増殖誘導法を用いた樹状細胞の大量産生 (2014)
  • Author(s): 今村悠哉、春田美和、冨田雄介、松村桂子、池田徳典、髙松孝太郎、西村泰治、千住覚
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 東京都
  • Year and Date: 2014-09-25
• [Presentation] HLA拘束性T細胞を誘導可能な末梢血モノサイト由来樹状細胞の大量産生法の開発 (2014)
  • Author(s): 今村悠哉、春田美和、冨田雄介、松村桂子、池田徳典、髙松孝太郎、西村泰治、千住覚
  • Organizer: 第23回日本組織適合性学会大会
  • Place of Presentation: 長崎市
  • Year and Date: 2014-09-14
• [Presentation] ヒトの末梢血単球の増殖誘導法を用いた樹状細胞の大量産生 (2014)
  • Author(s): 今村悠哉、春田美和、冨田雄介、松村桂子、池田徳典、髙松孝太郎、西村泰治、千住覚
  • Organizer: 第18回日本がん免疫学会総会
  • Place of Presentation: 松山市
  • Year and Date: 2014-08-01
• [Patent(Industrial Property Rights)] 血液由来単球の増殖誘導方法 (2016)
  • Inventor(s): 千住覚 今村祐哉
  • Industrial Property Rights Holder: 熊本大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-01-27