Development of antibody drugs targeting platelet activating receptor CLEC-2 and elucidation of the pharmacological actions
| Project/Area Number |
20K08729
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | University of Yamanashi |
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Principal Investigator |
Sasaki Tomoyuki 山梨大学, 大学院総合研究部, 准教授 (40739124)
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| Co-Investigator(Kenkyū-buntansha) |
井上 克枝 山梨大学, 大学院総合研究部, 教授 (10324211)
築地 長治 山梨大学, 大学院総合研究部, 講師 (20710362)
白井 俊光 山梨大学, 大学院総合研究部, 助教 (50710381)
大竹 志門 山梨大学, 大学院総合研究部, 助教 (50813060)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | CLEC-2 / 血小板 / 抗体医薬 |
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| Outline of Research at the Start |
本研究の目的は，抗血栓症及び抗癌転移作用等を期待できるCLEC-2を標的とした抗体医薬(抗CLEC-2抗体医薬)の開発とその抗体の作用メカニズムを含めた薬理作用の解明である．我々が目指す抗CLEC-2抗体医薬は，メカニズムに不明な点を残している特異な作用：『抗CLEC-2抗体が血小板CLEC-2を欠損させる作用』に基づいており，その不明点の解明と同時に開発研究を進める．薬剤としての安全性を担保するためには，作用の不明点を解明することは大変重要である．特異性が高く，免疫原性の低い安全で効果的な抗CLEC-2抗体医薬は，抗血栓や抗癌転移へのまったく新しい治療薬として期待できる．
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| Outline of Final Research Achievements |
The purpose of this study is to develop a clinically applicable anti-CLEC-2 drug, and to solve the problem of side effects such as thrombocytopenia caused by deletion or fragmentation of platelet activation ability by applying recent antibody modification technology based on the antibody already discovered. For this purpose, to enable functional modification of an existing antibody (clone name: 2A2B10), we have genetically modified it into a recombinant antibody and also into a mouse chimeric antibody, and have confirmed that the functions of the antibodies are equivalent. In addition, the yield was increased and the running cost was reduced by revising the gene transfer method. However, due to difficulties in epitope analysis, we were unable to reach the stage where we could begin modifying the antibody for use as an antibody drug.
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| Academic Significance and Societal Importance of the Research Achievements |
血小板CLEC-2の病態生理学的意義は、血小板血栓の形成に留まらず、血栓の安定化、癌の転移、肺発生、横紋筋融解症の重症化に寄与することが報告されている。血小板CLEC-2が治療標的となる疾患は拡大しており、有望な標的である。抗CLEC-2抗体のエピトープが判明したことは、今後の抗体医薬開発のための重要な情報である。
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Report
(4 results)
Research Products
(18 results)
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[Journal Article] Heme activates platelets and exacerbates rhabdomyolysis-induced acute kidney injury via CLEC-2 and GPVI/FcRγ2021
Author(s)
S. Oishi, N. Tsukiji, S. Otake, N. Oishi, T. Sasaki, T. Shirai, Y. Yoshikawa, K. Takano, H. Shinmori, T. Inukai, T. Kondo, K. Suzuki-Inoue
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Journal Title
blood advances
Volume: 5
Issue: 7
Pages: 2017-2026
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Role of Platelet C-Type Lectin-Like Receptor 2 in Promoting Lung Metastasis in Osteosarcoma2020
Author(s)
Jiro Ichikawa, Takashi Ando, Tomonori Kawasaki, Tomoyuki Sasaki, Toshiaki Shirai, Nagaharu Tsukiji, Yujiro Kimura, Kaoru Aoki, Keiko Hayakawa, Katsue Suzuki-Inoue, Masao Saitoh, Hirotaka Haro
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Journal Title
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Volume: in press
Issue: 9
Pages: 1738-1750
DOI
Related Report
Peer Reviewed
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[Presentation] 血小板受容体CLEC-2による関節リウマチの病態形成への関与2020
Author(s)
佐々木知幸, 白井俊光, 築地長治, 小山賢介, 田村彰吾, 大竹志門, 高野勝弘, 長田誠, 佐藤金夫, 波呂浩孝, 尾崎由基男, 井上克枝
Organizer
第42回日本血栓止血学会学術集会(2020.06.18)
Related Report
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