Development of therapeutic monoclonal antibodies aiming at an application and the immunosuppression to an allergic disease of Fingolimod

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K08409
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: International University of Health and Welfare
• Principal Investigator: YAGI HIDEKI 国際医療福祉大学, 薬学部, 教授 (40250740)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: FTY720 / S1P / 抗体 / 接触性過敏症

Outline of Final Research Achievements

For the purpose of clinical adaptation expansion of Fingolimod (FTY720) used as a therapeutic drug of the multiple sclerosis. We examined it in an animal model of oxazolone-induced contact hypersensitivity. Anti-inflammation effect to contact hypersensitivity was accepted by oral administration of 1 mg/kg of FTY720. This drug inhibited both effector T cell and dermis dendritic cell egress from the draining lymph node to the inflammatory lesion. On the other hand, the sphingosine 1-phosphate receptors (S1PR) considered to be target molecules of FTY720. The monoclonal antibody against mouse S1P4 were not available. We tried the production of anti-mouse S1P4 monoclonal antibody. We established three GFP-fusion mouse S1P4 receptor-expressing cells for immune cells. The rats were immunized by the mouse S1P4-expressing RH7777 cells. The antiserum of the immune rats got highly titer against mouse S1P4. However, we could not select hybridoma producing to mouse S1P4 monoclonal antibody.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

多発性硬化症の治療薬として用いられるフィンゴリモド（FTY720）の臨床適応拡大を目的に、アレルギー性接触性皮膚炎の動物モデルで、FTY720の1 mg/kgの経口投与で治療効果が認められた。これは、フィンゴリモドが細胞移動を伴うⅣ型アレルギーへの適用拡大ができる可能性を示したものである。メカニズムもエフェクターT細胞や真皮樹状細胞を感作付近のリンパ節にとどめ、炎症局所への移動を抑制することが示唆され、作用機序との整合性もあり、有望と考える。