Targeting myeloma progenitors by ex vivo-expanded gamma delta T cell

• Project/Area Number: 25860789
• 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, 大学病院, 助教 (50511333)
• Research Collaborator: NAKAMURA Shingen ; HARADA Takeshi
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 多発性骨髄腫 / γδT細胞 / lenalidomide

Outline of Final Research Achievements

Lenalidomide (Len) was able to expand γδ T cells more robustly in combination with HMB-PP than Zol from PBMCs from the majority of normal donors. However, Len alone did not show any significant effects on γδ T cell expansion and activation, suggesting a costimulatory role of Len on Zol or HMB-PP-primed γδ T cells. The surface expression of LFA-1, NKG2D, DNAM-1 and TRAIL were up-regulated in the expanded γδ T cells. Len in combination with either Zol or HMB-PP enhanced intracellular IFN-γ along with the surface NKG2D, suggesting robust induction of Th1-like γδ T cells by Len. Importantly, γδ T cells expanded with the combinatory treatments with Len and Zol or HMB-PP exerted potent cytotoxic activity against multiple myeloma (MM) cells. Interestingly, the expanded γδ T cells markedly suppressed the colony formation in RPMI8226 and KMS-11 cells, and decreased in size their side populations, suggesting targeting a drug-resistant clonogenic MM cells.

Research Products

• [Journal Article] Association of Th1 and Th2 cytokines with transient inflammatory reaction during lenalidomide plus dexamethasone therapy in multiple myeloma. (2013)
  • Author(s): Harada T, Ozaki S, Oda A, Fujii S, Nakamura S, Miki H, Kagawa K, Takeuchi K, Matsumoto T, Abe M.
  • Journal Title: Int J Hematol Volume: 97 Issue: 6 Pages: 743-748
  • DOI: 10.1007/s12185-013-1321-0
  • NAID: 10031183730
  • Peer Reviewed
• [Presentation] Targeting of myeloma progenitors by Th1-like gdT cells and hyperthermia (2014)
  • Author(s): 三木 浩和
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪国際会議場 大阪府 大阪市
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] 骨髄腫前駆細胞を標的としたレナリドミドにより増幅される Th1 様 gdT細胞療法の効果 (2014)
  • Author(s): 原田 武志
  • Organizer: 第39回日本骨髄腫学会学術集会
  • Place of Presentation: 掛川グランドホテル 静岡県 掛川市
  • Year and Date: 2014-05-17 – 2014-05-18
• [Presentation] Robust induction of Th1-like gdT cells with anti-myeloma activity by lenalidomide in combination with HMB-PP as well as zoledronic acid
  • Author(s): Takeshi Harada, Cui Qu, Shingen Nakamura, Hirokazu Miki, Asuka Oda, Ryota Amachi, Masami Iwasa, Kengo Udaka, Shiro Fujii, Kumiko Kagawa, Shuji Ozaki, Yoshimasa Tanaka, Toshio Matsumoto and Masahiro Abe
  • Organizer: The 55th Annual Meeting of the American Society of Hematology
  • Place of Presentation: Ernest N. Morial Convention Center, New Orleans, LA, USA