Effective expansion of Th1-like gdT cells and anti-myeloma effects

• Project/Area Number: 15K19551
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: The University of Tokushima
• Principal Investigator: MIKI Hirokazu 徳島大学, 病院, 講師 (50511333)
• Research Collaborator: FUJII Shiro
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 多発性骨髄腫 / γδＴ細胞 / 温熱療法 / 腫瘍前駆細胞 / γδT細胞

Outline of Final Research Achievements

After PBMCs isolated from 10 normal donors were incubated for one week with Zol and lenalidomide (LEN) or pomalidomide (POM) in combination, γδT cells were robustly expanded as observed with Zol and IL-2 in combination. The expanded γδT cells expressed intracellular IFN-γ but not Foxp3,indicating induction of Th1-like γδT cells.The expansion efficiency with Zol plus these IMiDs appeared to be weakerin PBMCs from a majority of patients with multiple myeloma (MM) than those from normal donors.Such expanded Th1-like γδT cells exerted potent cytotoxic activity against MM cells. Interestingly, the expanded γδT cells also markedly minimized the sizes of side populations in RPMI8226 and KMS-11 cells, and suppressed their clonogenic capacity. Hyperthermia induces MM cell death and and up-regulated the surface expression of HSP and ULBP on MM cells. These results suggest that hyperthermia might enhance the susceptibility of MM cells to γδT-mediated immunotherapy.

Research Products

• [Journal Article] Expansion of Th1-like Vγ9Vδ2T cells by new generation IMiDs, lenalidomide (2017)
  • Author(s): Takeshi Harada, Hirokazu Miki, Qu Cui, Asuka Oda, Ryota Amachi, Jumpei Teramachi, Ariunzaya Bat-Erdene, Kimiko Sogabe, Masami Iwasa, Shiro Fujii, Shingen Nakamura, Kumiko Kagawa, Sumiko Yoshida, Itsuro Endo, Kenichi Aihara, Shuji Ozaki, Toshio Matsumoto, Masahiro Abe
  • Journal Title: Leukemia Volume: 31 Pages: 258-262
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Expansion of γδT cells by new generation IMiDs and their cytotoxicity against myeloma progenitors (2016)
  • Author(s): 三木浩和
  • Organizer: 第58回米国血液学会
  • Place of Presentation: アメリカ、サンディエゴ
  • Year and Date: 2016-12-03
  • Int'l Joint Research
• [Presentation] Expansion of Th1-like γδT cells by lenalidomide or pomalidomide in combination with zoledronic acid (2016)
  • Author(s): 三木浩和
  • Organizer: 第78回日本血液学会学術集会
  • Place of Presentation: 神奈川県 横浜市 パシフィコ横浜
  • Year and Date: 2016-10-13
• [Presentation] 体外増幅Th1様 γδT細胞の骨髄腫前駆細胞への抗腫瘍効果 (2016)
  • Author(s): 三木浩和
  • Organizer: 第41回日本骨髄腫学会学術集会
  • Place of Presentation: 徳島県 徳島市 あわぎんホール
  • Year and Date: 2016-05-28
• [Presentation] Effective impairment of myeloma progenitors by ex-vivo expanded Th1-like γδT cells with hyperthermia (2016)
  • Author(s): 三木浩和
  • Organizer: 第7回日本血液学会国際シンポジウム
  • Place of Presentation: 兵庫県 淡路市 淡路夢舞台国際会議場
  • Year and Date: 2016-05-13
  • Int'l Joint Research
• [Presentation] Enhancement of myeloma cell drug susceptibility and targeting myeloma progenitors by hyperthermia (2015)
  • Author(s): Hirokazu Miki
  • Organizer: The 77th annual meeting of Japanese Society of Heatology
  • Place of Presentation: 金沢全日空ホテル 石川県金沢市
  • Year and Date: 2015-10-16
• [Presentation] Effective impairment of myeloma progenitors by hyperthermia : augumentation with bortezomib and Pim inhibition combination (2015)
  • Author(s): Hirokazu Miki
  • Organizer: The 15th International Myeloma Workshop
  • Place of Presentation: Rome Auditorium Parco and Musica Italy
  • Year and Date: 2015-09-23
  • Int'l Joint Research
• [Presentation] 温熱療法は薬剤耐性骨髄腫前駆細胞を効率的に障害する (2015)
  • Author(s): 三木 浩和
  • Organizer: 第40回日本骨髄腫学会学術集会
  • Place of Presentation: 熊本森都心プラザ 熊本県熊本市
  • Year and Date: 2015-05-16