Development of antibody drugs targeting platelet activating receptor CLEC-2 and elucidation of the pharmacological actions

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08729
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: University of Yamanashi
• Principal Investigator: Sasaki Tomoyuki 山梨大学, 大学院総合研究部, 准教授 (40739124)
• 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)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: CLEC-2 / 血小板 / 抗体医薬

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.

Free Research Field

血栓止血学

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。