The establishment of a research platform for the depression of ADAs production by Fab engineering.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16434
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Sojo University
• Principal Investigator: Nakamura Hitomi 崇城大学, 薬学部, 講師 (60510691)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ADAs / Fab / 安定化 / フレームワーク領域

Outline of Final Research Achievements

Depression of anti-drug antibodies (ADAs) production is an important issue for the efficacy and safety of therapeutic antibodies. We previously reported that the structural stabilization of protein antigens leads to depression of the antibody production. In this study, we examined the correlation between conformational stability of protein and the amount of antibody production against antigen in mice using Fab to prove whether our findings are applied to engineered Fab. The Fab was successfully stabilized by introducing hydrophobic amino acids in the framework region, and the results of the immunization experiment with wild-type and mutated Fabs suggested that the more stable Fab tended to depress the antibody production.

Free Research Field

蛋白質工学、生化学

Academic Significance and Societal Importance of the Research Achievements

抗体医薬品は、がんや自己免疫疾患の治療に欠かせない存在となっており、今後も市場規模の拡大が予想されている。抗体医薬品はその性質上、ADAs産生の問題が避けられず、これを評価するための研究が活発に行われている一方で、抗体そのものの改変によるADAs産生抑制に関する報告はまだ少ない。本研究課題ではFabの安定化デザインに加えて、これまでに我々が基礎研究で見出してきた知見をADAs産生抑制へと応用できる可能性が示され、抗体医薬品の有効性と安全性の確保に貢献できるのではないかと考えている。