Control of inhibitory immunoreceptor in cell therapy after allogeneic hematopoietic stem cell transplantation

• Project/Area Number: 25461446
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Nagoya University
• Principal Investigator: NISHIDA Tetsuya 名古屋大学, 医学部附属病院, 助教 (80508929)
• Co-Investigator(Kenkyū-buntansha): ITO Yoshinori 名古屋大学, 医学系研究科, 准教授 (20373491)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 免疫抑制受容体 / 抗原特異的T細胞 / 抗原提示細胞 / 細胞療法 / 樹状細胞 / 人工抗原提示細胞 / ウイルス抗原特異的T細胞 / 同種造血幹細胞移植

Outline of Final Research Achievements

Adenovirus serotype 11 (AdV-11) occasionally causes hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation. A novel T-cell epitope (TYFNLGNKF) of AdV-11 presented by HLA-A*24:02 was identified, and the epitope indeed functions as a target for TYFNLGNKF-specific T cells in vivo. It was demonstrated that antigen-specific T cells could be generated rapidly and efficiently by the use of anti-4-1BB antibody without antigen-presenting cells. And PD-L1 expressed on antigen-presenting cells along with CD80/86 showed to enhance the induction of antigen-specific T cells. These findings are applicable to cell therapy in the future.

Research Products

• [Journal Article] Simple and Efficient Generation of Virus-specific T Cells for Adoptive Therapy Using Anti-4-1BB Antibody (2015)
  • Author(s): Nobuhiko Imahashi, Tetsuya Nishida, Tatsunori Goto, Seitaro Terakura, Keisuke Watanabe, Ryo Hanajiri, Reona Sakemura, Misa Imai, Hitoshi Kiyoi, Tomoki Naoe, and Makoto Murata
  • Journal Title: Journal of Immunotherapy Volume: 38(2) Issue: 2 Pages: 62-70
  • DOI: 10.1097/cji.0000000000000069
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Correlations of programmed death 1 expression and serum IL-6 level with exhaustion of cytomegalovirus-specific T cells after allogeneic hematopoietic stem cell transplantation (2014)
  • Author(s): Kato T, Nishida T, Ito Y, Murase M, Murata M, Naoe T
  • Journal Title: Cellular Immunology Volume: 288 Issue: 1-2 Pages: 53-59
  • DOI: 10.1016/j.cellimm.2014.02.007
  • Peer Reviewed
• [Journal Article] Identification of a novel HLA-A^*24:02-restricted adenovirus serotype 11-specific CD8+ T-cell epitope for adoptive immunotherapy (2013)
  • Author(s): Imahashi N, Nishida T, Ito Y, Kawada J, Nakazawa Y, Toji S, Suzuki S, Terakura S, Kato T, Murata M, Naoe T.
  • Journal Title: Molecular Immunolgy Volume: 56 Issue: 4 Pages: 399-405
  • DOI: 10.1016/j.molimm.2013.05.232
  • Peer Reviewed
• [Presentation] PD-L1 on Antigen-Presenting Cells Facilitate the Induction of Antigen-Specific Cytotoxic T Lymphocytes (2015)
  • Author(s): Goto T, Nishida T, Takagi E, Miyao K, Koyama D, Sakemura R, Hanajiri R, Watanabe K, Imahashi N, Terakura S, Murata M, Kiyoi H
  • Organizer: 57th American Society of Hematology Annual Meeting and Exposition
  • Place of Presentation: 米国、オーランド
  • Year and Date: 2015-12-05
  • Int'l Joint Research
• [Presentation] Roles of PD-L1 on antigen-presenting cells for the generation of antigen-specific T cells (2015)
  • Author(s): 後藤辰徳、西田徹也、高木えり奈、宮尾康太郎、小山大輔、酒村玲央奈、葉名尻良、渡邊慶介、今橋伸彦、寺倉 精太郎、村田誠、清井仁
  • Organizer: 第77回日本血液学会学術集会
  • Place of Presentation: 石川県金沢市 ホテル日航金沢
  • Year and Date: 2015-10-16
• [Presentation] 非血縁者間骨髄移植後難治性CMV感染に対してCMV抗原特異的CTLが著効した2症例 (2014)
  • Author(s): 西田徹也、村田誠、寺倉精太郎、勝見章、直江知樹
  • Organizer: 第36回日本造血細胞移植学会
  • Place of Presentation: 沖縄コンベンションセンター(宜野湾市）