The new technology to generate dendritic cells with natural killer cell activity

• Project/Area Number: 24501330
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor immunology
• Research Institution: Shinshu University
• Principal Investigator: SHIMODAIRA Shigetaka 信州大学, 学術研究院医学系(医学部附属病院), 准教授 (80345751)
• Co-Investigator(Renkei-kenkyūsha): NISHIMURA Takashi 北海道大学, 遺伝子病制御研究所, 教授 (30143001)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 樹状細胞 / キラー活性 / がん免疫療法 / インターフェロン / G-CSF / がんワクチン / Ｇ－ＣＳＦ / ＭＭＰ－９ / 腫瘍抗原ペプチド / 担癌モデルマウス / 接着因子

Outline of Final Research Achievements

Dendritic cell (DC)-based immunotherapy has been developed against various types of cancers as an active immunotherapy. Cancer vaccination therapies with autologous monocyte-derived mature DCs are principally attributed to the presence of tumor-associated antigens.
The following issues for clinical use may be raised: 1) Manufacturing of DCs; 2) Peptides that target cancer-associated antigens for any cancer patient; 3) Quality of immunological analyses as proof of concept; and 4) Optimization of DC vaccines as add-ons to chemotherapeutic drugs and/or radiotherapy.
Different from the conventional adherent system for GM-CSF and IL-4, the new technology has been progressed to generate DCs induced by interferon (IFN) with natural killer cell activity (killer-DC). This would contribute to the development of future cancer vaccination technology in Japan.

Research Products

• [Journal Article] Smoking influences the yield of dendritic cells for cancer immunotherapy. (2015)
  • Author(s): Shimodaira S, Higuchi Y, Koya T, Kobayashi T, Yanagisawa R, Hirabayashi K, Ito K, Koizumi T, Maejima S, Udagawa N.
  • Journal Title: Pharmaceut Reg Affairs Volume: 4 Issue: 01 Pages: 1-1
  • DOI: 10.4172/2167-7689.1000133
  • Peer Reviewed / Open Access
• [Journal Article] Safety and tolerability of allogeneic dendritic cell vaccination with induction of WT1-specific T cells in a pediatric donor and pediatric patient with relapsed leukemia: A case report and review of the literature. (2015)
  • Author(s): Saito S, Yanagisawa R, Yoshikawa K, Higuchi Y, Koya T, Yoshizawa K, Tanaka M, Sakashita K, Kobayashi T, Kurata T, Hirabayashi K, Nakazawa Y, Shiohara M, Yonemitsu Y, Okamoto M, Sugiyama S, Koike K, Shimodaira S.
  • Journal Title: Cytotherapy Volume: 17 Issue: 3 Pages: 330-335
  • DOI: 10.1016/j.jcyt.2014.10.003
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Therapeutic effect of intratumoral injections of dendritic cells for locally recurrent gastric cancer: a case report. (2014)
  • Author(s): Kobayashi M, Sakabe T, Chiba A, Nakajima A, Okamoto M, Shimodaira S, Yonemitsu Y, Shibamoto Y, Suzuki N, Nagaya M.
  • Journal Title: World J Surg Oncol Volume: 12 Issue: 1 Pages: 390-390
  • DOI: 10.1186/1477-7819-12-390
  • Peer Reviewed
• [Journal Article] The feasibility and clinical effects of dendritic cell-based immunotherapy targeting synthesized peptides for recurrent ovarian cancer. (2014)
  • Author(s): Kobayashi M, Chiba A, Izawa H, Yanagida E, Okamoto M, Shimodaira S, Yonemitsu Y, Shibamoto Y, Suzuki N, Nagaya M; The DC-vaccine study group at the Japan Society of Innovative Cell Therapy (J-SICT).
  • Journal Title: J Ovarian Res Volume: 7 Issue: 1 Pages: 48-48
  • DOI: 10.1186/1757-2215-7-48
  • Peer Reviewed / Open Access
• [Journal Article] Treatment with chemotherapy and dendritic cells pulsed with multiple Wilms' tumor 1 (WT1)-specific MHC class I/II-restricted epitopes for pancreatic cancer. (2014)
  • Author(s): Koido S, Homma S, Okamoto M, Takakura K, Mori M, Yoshizaki S, Tsukinaga S, Odahara S, Koyama S, Imazu H, Uchiyama K, Kajihara M, Arakawa H, Misawa T, Toyama Y, Yanagisawa S, Ikegami M, Kan S, Hayashi K, Komita H, Kamata Y, Ito M, Ishidao T, Yusa S, Shimodaira S, Gong J, Sugiyama H, Ohkusa T, Tajiri H.
  • Journal Title: Clin Cancer Res Volume: 20 Pages: 4228-39
  • Peer Reviewed
• [Journal Article] Prognostic factors related to add-on dendritic cell vaccines on patients with inoperable pancreatic cancer receiving chemotherapy: a multicenter analysis. (2014)
  • Author(s): Kobayashi M, Shimodaira S, Nagai K, Ogasawara M, Takahashi H, Abe H, Tanii M, Okamoto M, Tsujitani S, Yusa S, Ishidao T, Kishimoto J, Shibamoto Y, Nagaya M, Yonemitsu Y; DC Vaccine Study Group at the Japan Society of Innovative Cell Therapy (J-SICT).
  • Journal Title: Cancer Immunol Immunother Volume: 63 Issue: 8 Pages: 797-806
  • DOI: 10.1007/s00262-014-1554-7
  • Peer Reviewed
• [Journal Article] Dendritic cell-based immunotherapy targeting synthesized peptides for advanced biliary tract cancer (2013)
  • Author(s): Kobayashi M, Sakabe T, Abe H, Tanii M, Takahashi H, Chiba A, Yanagida E,Shibamoto Y, Ogasawara M, Tsujitani S, Koido S, Nagai K, Shimodaira S, Okamoto M,Yonemitsu Y, Suzuki N, Nagaya M; DC-vaccine study group at the Japan Society of Innovative Cell Therapy (J-SICT).
  • Journal Title: J Gastrointest Surg Volume: 17(9) Issue: 9 Pages: 1609-17
  • DOI: 10.1007/s11605-013-2286-2
  • Peer Reviewed
• [Journal Article] Immunochemoradiotherapy for patients with oral squamous cell carcinoma: augmentation of OK-432-induced helper T cell 1 response by 5-FU and X-ray irradiation (2013)
  • Author(s): Tano T, Okamoto M, Kan S, Bando T, Goda H, Nakashiro K, Shimodaira S, Koido S, Homma S, Fujita T, Sato M, Yamashita N, Hamakawa H, Kawakami Y
  • Journal Title: Neoplasia Volume: 15 Pages: 805-14
  • Peer Reviewed
• [Journal Article] Prognostic impact of expression of Bcl-2 and Bax genes in circulating immune cells derived from patients with head and neck carcinoma. (2013)
  • Author(s): Tano T, Okamoto M, Kan S, Nakashiro K, Shimodaira S, Koido S, Homma S, Sato M, Fujita T, Kawakami Y, Hamakawa H.
  • Journal Title: Neoplasia Volume: 15 Pages: 305-14
  • Peer Reviewed
• [Journal Article] Eur J Cancer (2013)
  • Author(s): Hidenori Takahashi
  • Journal Title: 10.1016/j.ejca.2012.11.005 Volume: 49 Issue: 4 Pages: 852-859
  • DOI: 10.1016/j.ejca.2012.11.005
  • Peer Reviewed
• [Journal Article] Growth inhibition and apoptosis by an active component of OK-432, a streptococcal agent, via Toll-like receptor 4 in human head and neck cancer cell lines (2012)
  • Author(s): Tano T
  • Journal Title: Oral Oncology Volume: 48 Issue: 8 Pages: 678-85
  • DOI: 10.1016/j.oraloncology.2012.02.005
  • Peer Reviewed
• [Journal Article] Clinical and immunologic evaluation of dendritic cell-based immunotherapy in combination with gemcitabine and/or S-1 in the patients with advanced pancreatic carcinoma (2012)
  • Author(s): Kimura Y, et al
  • Journal Title: Pancreas Volume: 41 Issue: 2 Pages: 195-205
  • DOI: 10.1097/mpa.0b013e31822398c6
  • Peer Reviewed
• [Presentation] Dendritic cell-based Cancer Immunotherapy (2015)
  • Author(s): Shigetaka Shimodaira
  • Organizer: 3rd International Conference on Hematology& Blood Disorders
  • Place of Presentation: Atlanta, USA
  • Year and Date: 2015-11-02 – 2015-11-04
  • Invited
• [Presentation] Safety and tolerability of allogeneic dendritic cell vaccination targeting Wilms’ tumor 1 (2015)
  • Author(s): Shigetaka Shimodaira
  • Organizer: 16th Royan International Research Award
  • Place of Presentation: Tehran, IRAN
  • Year and Date: 2015-09-02 – 2015-09-04
  • Invited
• [Presentation] 再生医療等の安全性の確保等に関する法律に対応した樹状細胞製剤の評価に関する検討 (2015)
  • Author(s): 小屋照継，樋口由美子，湯沢美紀，水野由美子，山岡直子，曽根田美樹，堀内香与，平林耕一，小林孝至，下平滋隆
  • Organizer: 第14回 日本再生医療学会総会
  • Place of Presentation: 横浜 （パシフィコ横浜）
  • Year and Date: 2015-03-21
• [Presentation] 樹状細胞及び腫瘍抗原ペプチドを用いたがんワクチン療法 (2014)
  • Author(s): 下平滋隆
  • Organizer: 第62回 日本輸血・細胞治療学会総会
  • Place of Presentation: 奈良 （奈良県新公会堂）
  • Year and Date: 2014-05-17
• [Presentation] 空路搬送に伴うＸ線検査がWT1ペプチドに及ぼす影響 (2014)
  • Author(s): 樋口由美子, 高橋香織, 吉澤清司, 小屋照継, 川久保雅友, 下平滋隆
  • Organizer: 第62回 日本輸血・細胞治療学会総会
  • Place of Presentation: 奈良 （奈良県文化会館）
  • Year and Date: 2014-05-16
• [Presentation] Cancer treatment with dendritic cells for patients visited from Kuwait
  • Author(s): Shigetaka Shimodaira
  • Organizer: The Forum of the Japan-UAE Joint Meeting for Cooperative promotion of Life Science
  • Place of Presentation: Tokyo, Japan
  • Invited
• [Presentation] 将来の樹状細胞及び腫瘍抗原ペプチドを用いたがんワクチン療法
  • Author(s): 下平 滋隆
  • Organizer: 第51回癌治療学会学術集会
  • Place of Presentation: 京都
  • Invited
• [Presentation] Harvesting the seeds of translational research: A clinical trial of dendritic cell based vaccination.
  • Author(s): Shigetaka Shimodaira
  • Organizer: 12th International Symposium on dendritic cells
  • Place of Presentation: Daegu, Korea
  • Invited
• [Remarks] 信州大学 学術情報オンラインシステムＳＯＡＲ
  • URL: http://www.shinshu-u.ac.jp/soar/
• [Patent(Industrial Property Rights)] IFNを用いた非接着培養による樹状細胞の調製方法 (2015)
  • Inventor(s): 下平滋隆，小屋照継
  • Industrial Property Rights Holder: 国立大学法人信州大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2015-053804
  • Filing Date: 2015-03-17
• [Patent(Industrial Property Rights)] G-CSFを用いた樹状細胞の調製方法 (2013)
  • Inventor(s): 下平滋隆、樋口由美子、小屋 照継
  • Industrial Property Rights Holder: 信州大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2012-028118
  • Filing Date: 2013-02-15
• [Patent(Industrial Property Rights)] 分離装置 (2013)
  • Inventor(s): 下平滋隆
  • Industrial Property Rights Holder: 信州大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-03-22
  • Overseas
• [Patent(Industrial Property Rights)] 血液成分分離装置 (2013)
  • Inventor(s): 下平滋隆
  • Industrial Property Rights Holder: 信州大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-03-22
  • Overseas
• [Patent(Industrial Property Rights)] 分離装置 (2012)
  • Inventor(s): 下平滋隆
  • Industrial Property Rights Holder: 信州大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2012-086514
  • Filing Date: 2012-04-05
• [Patent(Industrial Property Rights)] 分離装置 (2012)
  • Inventor(s): 下平滋隆
  • Industrial Property Rights Holder: 信州大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2012-086515
  • Filing Date: 2012-04-05