Modified anti-CD3 as a therapeutic antibody for lupus

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10001
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Osaka University
• Principal Investigator: Mizui Masayuki 大阪大学, 医学系研究科, 講師 (30423106)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 抗CD3サイレント抗体 / SLE / 自己抗体 / 臓器障害

Outline of Final Research Achievements

Modulating functions of autoreactive T-lymphocytes could be a therapeutic strategy for autoimmune diseases including systemic lupus erythematosus. Anti-CD3 silent antibody, which lacks binding activity both to complement and to Fc receptor, can induce down-regulation of T cell receptor (TCR). To address the efficacy of anti-CD3 silent antibody for the treatment of autoimmune diseases, the antidody was injected intraperitoneally once a week for 4 times into lupus prone NZB/W F1 mice at the age of 10 weeks or 20 weeks. As a result, we found that anti-double strand DNA antibody was reduced in mice of younger age with the suppression of differentiation of T follicular helper cells. Furthermore, when mice were treated at the age of 20 weeks, tissue damages such as lung and kidney were significantly attenuated with the association of reduced infiltration of inflammatory cells. Taken together, we propose that anti-CD3 silent antibody could have therapeutic potential for SLE.

Free Research Field

臨床免疫アレルギー学

Academic Significance and Societal Importance of the Research Achievements

抗CD3サイレント抗体は、TCR発現を低下させることにより、SLE早期では自己抗体産生を、中後期においては臓器の炎症惹起を抑制することにより、自己免疫疾患を改善させることが示唆された。ヒトにおける当該抗体はすでに存在しており、これらのメカニズムをさらに詳細に検討し解明することで、近い将来臨床応用が期待できる。