Elucidation of the function of the newly discovered NK cell subset and its application to adoptive immunotherapy

• Project/Area Number: 18H04060
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
• Research Institution: Kyushu University
• Principal Investigator: YONEMITSU YOSHIKAZU 九州大学, 薬学研究院, 教授 (40315065)
• Co-Investigator(Kenkyū-buntansha): 原田 結 九州大学, 薬学研究院, 准教授 (00608507)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥45,240,000 (Direct Cost: ¥34,800,000、Indirect Cost: ¥10,440,000); Fiscal Year 2020: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000); Fiscal Year 2019: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000); Fiscal Year 2018: ¥26,520,000 (Direct Cost: ¥20,400,000、Indirect Cost: ¥6,120,000)
• Keywords: NK細胞 / Licensing / 固形腫瘍 / 養子免疫 / 再生医療等製品 / 免疫療法 / ライセンシング / NK細胞、ライセンシング

Outline of Final Research Achievements

We analyzed the biological significance of NK cell-like cells (development code: GAIA-102), which we independently discovered and started clinical development as a cell-based medicine, especially from the viewpoint of their properties as "Emergency NK". The characteristic chemokine / chemokine receptor expression, gene expression pattern, and similarity to Memory-like NK have revealed a part of the mechanism by which these cells have high cytotoxic activity especially against solid tumors in vivo/in vitro. We believe that the above findings will be the basis for demonstrating clinical effectiveness.

Academic Significance and Societal Importance of the Research Achievements

特に固形腫瘍を対象とする養子免疫療法としての実用化を目指す上で、GAIA-102のような特異な形質（固形腫瘍の傷害能がin vitro/in vivoで共に極めて高い）を持つ細胞の特性を解析することは、有効性および安全性の観点から意義深い。本研究の最終目標であるGAIA-102の正体解明は、社会的に大きな課題である悪性腫瘍に対する治療体系に変革をもたらし得ると考える。悪性腫瘍を根治させることが可能な免疫治療がもたらしたパラダイムシフトは今後、さらに免疫の理解によって利用が促進されることを想定し、重要なエフェクターの一つであるNK細胞のバイオロジーを紐解く意味でも社会的意義は大きい。

Research Products

• [Journal Article] Fc-binding antibody-recruiting molecules targeting prostate-specific membrane antigen: defucosylation of antibody for efficacy improvement (2021)
  • Author(s): Sasaki K, Harada M, Yoshikawa T, Tagawa H, Harada Y, Yonemitsu Y, Ryujin T, Kishimura A, Mori T, Katayama Y.
  • Journal Title: ChemBioChem Volume: 22 Issue: 3 Pages: 496-500
  • DOI: 10.1002/cbic.202000577
  • Peer Reviewed / Open Access
• [Journal Article] Highly activated ex vivo-expanded natural killer cells in patients with solid tumors in a Phase I/IIa clinical study (2020)
  • Author(s): Nagai K, Harada Y, Harada H, Yanagihara K, Yonemitsu Y, Miyazaki Y.
  • Journal Title: Anticancer Res. Volume: 40 Issue: 10 Pages: 5687-5700
  • DOI: 10.21873/anticanres.14583
  • Peer Reviewed
• [Presentation] GAIA-102: 固形腫瘍に対する新規革新的細胞製剤 (2020)
  • Author(s): Harada Y, Yonemitsu Y.
  • Organizer: 第24回日本がん免疫学会 (札幌/オンライン)
• [Presentation] GAIA-102: a new class off-the-shelf allogeneic NK-like cells that can eliminate solid tumors (2020)
  • Author(s): Harada Y, Yonemitsu Y.
  • Organizer: Society for Immunotherapy of Cancer (SITC) 35th Anniversary Annual Meeting (Washington DC/On-line)
  • Int'l Joint Research
• [Presentation] 機能を持つ新生血管の誘導：メカニズム解析からトランスレーショナルリサーチへ (2019)
  • Author(s): 米満吉和
  • Organizer: 第47回日本血管外科学会学術集会
• [Presentation] DVC1-0101- An RNA gene drug based on recombinant Sendai virus to treat peripheral arterial disease (2019)
  • Author(s): Yoshikazu Yonemitsu
  • Organizer: International Gene and Cell therapy Symposium
  • Int'l Joint Research / Invited
• [Presentation] DVC1-0101- An RNA gene drug based on recombinant Sendai virus to treat peripheral arterial disease (2019)
  • Author(s): Yoshikazu Yonemitsu
  • Organizer: 25th Annual Meeting of Japan Society of Gene and Cell Therapy
• [Presentation] PADにおける薬物療法と血管新生療法：エビデンス集積の現状 (2019)
  • Author(s): 米満吉和
  • Organizer: 第60回日本脈管学会総会
• [Presentation] GAIA-102: A novel natural killer cell-like phenotype that can eliminate solid tumor. (2019)
  • Author(s): Yoshikazu Yonemitsu
  • Organizer: 27th Annual Meeting of European Society of Gene and Cell Therapy
  • Int'l Joint Research / Invited
• [Presentation] AdoptCell(R)-NK: a new class NK cells manufactured in accordance with GMP/GCTP that can eliminate the solid tumors (2019)
  • Author(s): Yonemitsu Y,Harada Y.
  • Organizer: The 3rd Innate Killer Summit (San Diego)
• [Presentation] CAR-T vs. NK：固形がん養子免疫治療にはどちらが適しているか？ (2018)
  • Author(s): 米満吉和
  • Organizer: 第7回日本免疫・細胞治療学会 学術総会
• [Presentation] AdoptCell (R)-NK: a Novel Natural Killer Cell Phenotype That Can Eliminate the Solid Tumors (2018)
  • Author(s): Yonemitsu Y,Harada Y.
  • Organizer: American society of Gene and Cell Therapy 21st Annual meeting (Chicago)
• [Presentation] GAIA-102: a new class NK cells manufactured in accordance with GMP/GCTP that can eliminate the solid tumors (2018)
  • Author(s): Yonemitsu Y,Harada Y.
  • Organizer: The 24th Annual Meeting of JSGCT（東京）
• [Presentation] AdoptCell(R)-NK: a new class NK cells manufactured in accordance with GMP/GCTP that can eliminate the solid tumors (2018)
  • Author(s): Yonemitsu Y,Harada Y.
  • Organizer: Society for Immunotherapy of Cancer (SITC) 33rd Anniversary Annual Meeting (Washington DC)
• [Presentation] Development of innovative therapeutics for solid tumors (2018)
  • Author(s): Yonemitsu Y,Harada Y.
  • Organizer: The 29th Annual Meeting of the Japanese Society for Gastroenterological Carcinogenesis （東京）
• [Patent(Industrial Property Rights)] 高活性ＮＫ細胞の処理方法 (2020)
  • Inventor(s): 原田 結、米満吉和
  • Industrial Property Rights Holder: 原田 結、米満吉和
  • Industrial Property Rights Type: 特許
  • Filing Date: 2020
• [Patent(Industrial Property Rights)] 高活性NK細胞、およびその利用 (2019)
  • Inventor(s): 米満吉和、原田 結
  • Industrial Property Rights Holder: 原田 結
  • Industrial Property Rights Type: 特許
  • Filing Date: 2019
  • Acquisition Date: 2019