2022 Fiscal Year Research-status Report
Natural Killer (NK) Cell Immunotherapy Towards Adult T Cell Leukemia (ATL) via Exaltation of MICA/B Expression and Augments NK Cytotoxicity
| Project/Area Number |
22K16327
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| Research Institution | Kumamoto University |
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Principal Investigator |
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)
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| Project Period (FY) |
2022-04-01 – 2024-03-31
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| Keywords | ATL / iMIDs / NK sensitization |
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| Outline of Annual Research Achievements |
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.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
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.
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| Strategy for Future Research Activity |
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.
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| Causes of Carryover |
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.
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