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2022 年度 実施状況報告書

Natural Killer (NK) Cell Immunotherapy Towards Adult T Cell Leukemia (ATL) via Exaltation of MICA/B Expression and Augments NK Cytotoxicity

研究課題

研究課題/領域番号 22K16327
研究機関熊本大学

研究代表者

Panaampon Jutatip  熊本大学, ヒトレトロウイルス学共同研究センター, 客員助教 (60868313)

研究期間 (年度) 2022-04-01 – 2024-03-31
キーワードATL / iMIDs / NK sensitization
研究実績の概要

We checked MICA/B expression on various ATL cell lines (ED-, TL-Om1, S1T, KK-1, LMHW5, OATL-4, and SU9T1). We found ED- and TL-Om1 express high MICA/B on cell surface whereas S1T cell shows very low/no MICA/B expression. We used ED-, TL-Om1 as representative MICA/Bhigh ATL and S1T as MICA/Bno ATL. We then test S1T, ED-, and TL-Om1 for NK cytotoxicity and found that S1T cells which have very low MICA/B expression, resist to NK cell cytotoxicity whereas ED-, and TL-Om1 are sensitive to NK cytotoxicity. The results suggest that MICA/B, which is NKG2D ligand is crucial for NK cell cytotoxicity.
We demonstrate iMIDs increase MICA/B expression on ATL. We tested the efficacy of iMIDs treatment for MICA/B expression. Lenalidomide, Pomalidomide, Iberdomide, CC-92480 were tested in this study. The noncytotoxic doses were tested with ATL. Among all of those, CC-92480 show highest efficacy to enhance MICA/B expression. By using primary NK cells from healthy donor, we found that Lenalidomide, Pomalidomide, Iberdomide and CC-92480 sensitized ATL to NK cytotoxicity and CC-92480 displayed the highest efficacy among iMIDs.

現在までの達成度 (区分)
現在までの達成度 (区分)

2: おおむね順調に進展している

理由

We are doing the process of MICA/B overexpression on S1T and knockdown MICA/B on ED- cells and tested to confirm MICA/B is crucial for NK sensitization. Moreover, we are working on more NK donors.

今後の研究の推進方策

We will use ATL- bearing immunodeficient mice to study NK cell adoptive transfer and tumor control. We will test different ATLs that have different level of MICA/B expression and observe the correlation of MICA/Bhigh or MICA/Blow and tumor burden after NK adoptive transfer.

次年度使用額が生じた理由

I did not use Article costs this year as we could use the antibodies etc. we had in our Laob. As I used up these antibodies, I will buy antibodies and the reagents we use in 2023. I am planning to publish our data in 2023 which need article processing fee.

  • 研究成果

    (3件)

すべて 2023 2022

すべて 雑誌論文 (2件) 学会発表 (1件) (うち国際学会 1件)

  • [雑誌論文] Dihydroartemisinin Induced Apoptosis and Synergized With Chemotherapy in Pleural Effusion Lymphoma Cells2023

    • 著者名/発表者名
      PHIKULSOD PLOYPLOEN、KARIYA RYUSHO、PANAAMPON JUTATIP、OKADA SEIJI
    • 雑誌名

      Anticancer Research

      巻: 43 ページ: 1139~1148

    • DOI

      10.21873/anticanres.16259

  • [雑誌論文] Elotuzumab, a potential therapeutic humanized anti-SLAMF7 monoclonal antibody, enhances natural killer cell-mediated killing of primary effusion lymphoma cells2022

    • 著者名/発表者名
      Panaampon Jutatip、Kariya Ryusho、Okada Seiji
    • 雑誌名

      Cancer Immunology, Immunotherapy

      巻: 71 ページ: 2497~2509

    • DOI

      10.1007/s00262-022-03177-6

  • [学会発表] TKM-011, Anti-CD20 Antibody Confers Multi-Properties Against Burkitt’s Lymphoma in Comparable Efficacy to Rituximab and Obinutuzumab2022

    • 著者名/発表者名
      Jutatip Panaampon and Seiji Okada
    • 学会等名
      37th Annual Meeting of The Society for Immunotherapy of Cancer
    • 国際学会

URL: 

公開日: 2023-12-25  

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