| Project/Area Number |
17K15762
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Applied pharmacology
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| Research Institution | Shujitsu University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | L-アスパラギナーゼ / L-asparaginase / 薬物アレルギー / アレルギー / 小児白血病 / 急性リンパ性白血病 / オマリズマブ / 中和抗体 / L-asparaginese / モデル動物 |
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| Outline of Final Research Achievements |
L-Asparaginase (L-ASP) is a key drug in the treatment of childhood acute lymphoblastic leukemia. L-ASP often causes hypersensitivity reactions. However, the characteristics of L-ASP-induced hypersensitivity are not well documented so far. Also, there is neither suitable treatment for L-ASP allergy nor adequate experimental model of L-ASP allergy.
In this study, we used RBL-2H3 mast cells to establish in vitro model of L-ASP allergy. Furthermore, we evaluated the effect of anti-IgE antibody (Ab) on L-ASP allergy in vitro.
When RBL-2H3 cells were sensitized by L-ASP-sensitized mouse serum in vitro, L-ASP induced degranulation from the cells. Anti-IgE Ab effectively inhibited the allergic activation of RBL-2H3 cells. From the present results, it became clear that anti-IgE Ab is a useful drug for the treatment of L-ASP allergy. Using cell lines expressing human FcεRI, it can be possible to diagnose L-ASP allergy in human and efficacy of anti-IgE Ab in vitro.
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| Academic Significance and Societal Importance of the Research Achievements |
小児の病死の死因1位はがんであり、その中でも小児急性リンパ性白血病（ALL）は最も多く占める。L-アスパラギナーゼ（L-ASP）は、小児ALLの標準治療であるため、本研究によりL-ASPアレルギーの病態解明や治療薬の開発が進むことで、L-ASPアレルギーの克服が可能となり、多数の小児がん患者を救うことが期待出来る。さらに、本研究で得られた知見をもとに、他の薬物アレルギーの克服にも役立てることが出来る。
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