Development of a hybridized catalytic antibody regulating the function of cancer-related proteins

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K21255
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 37:Biomolecular chemistry and related fields
• Research Institution: Oita University
• Principal Investigator: HIFUMI EMI 大分大学, 研究マネジメント機構, 教授 (90254606)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Keywords: 抗体酵素 / 免疫チェックポイント / PD-1 / PD-L1 / 抗体軽鎖

Outline of Final Research Achievements

T-cells are existing in our body and play a role in attacking cancer and/or abnormal cells. When these T cells are kept in an activated state, they can attack and eliminate cancer cells regardless of the type of cancer. However, some cancer cells express a ligand PD-L1 to avoid from attacking of T cells. Once T-cells are inactivated by PD-L1, they cannot suppress the proliferation of cancer cells, resulted in the progression of the disease. In this study, we advanced the production of catalytic antibody targeting both PD-1 on T cells and PD-L1 on cancer cells by using our unique technology. As the results, we succeeded in the production of a hybridized catalytic antibody to simultaneously degrade both PD-1 and PD-L1 molecules. In addition, the catalytic antibody produced in this study possessed a new active site and expanded the potential of application of catalytic antibody.

Free Research Field

抗体工学

Academic Significance and Societal Importance of the Research Achievements

複数のがん関連タンパク質を同時に制御する革新的な「機能性分子標的薬」の創出に繋がり、新ジャンルを切り開く先駆けとなる技術である。標的タンパク質（抗原）を変えることで、標的分子型の抗体医薬は勿論のこと、感染症や自己免疫疾患などの幅広い疾患に適用出来る。ADCC活性やCDC活性を必要としないので、生体外での使用も可能となるのに加えて、通常の抗体よりもピンポイントで標的を絞り込み、抗原を不活化する事が可能であるため、例えばRNAウイルスの保存領域などの重要・かつ極めて狭い（限られた）領域もターゲットとして扱うことが出来る。