Development of innovative therapy for autoantibody-related disorders using fusion proteins combining IgG1Fc and extracellular domains of target antigen.

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19438
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 52:General internal medicine and related fields
• Research Institution: Chiba University
• Principal Investigator: Masahiro Mori 千葉大学, 大学院医学研究院, 准教授 (70345023)
• Co-Investigator(Kenkyū-buntansha): 鵜沢 顕之 千葉大学, 医学部附属病院, 助教 (10533317) ; 桑原 聡 千葉大学, 大学院医学研究院, 教授 (70282481)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: 視神経脊髄炎 / アクアポリン４ / 融合タンパク / B細胞

Outline of Final Research Achievements

To prove the hypothesis that administration of fusion proteins combining IgG1 Fc region and extracellular domains of target aquaporin-4(AQP4) can ameliorate neuromyelitis optica (NMO) by neutralization of anti-AQP4 antibodies and antibody-mediated cytotoxicity against anti-AQP4 antibody-producing B cells in AQP4-IgG-positive neuromyelitis, We tried to make a fusion protein (AQP4loopX-Fc) of the extracellular region of AQP4 and the IgG1 Fc region. After the amino acid sequences of the extracellular region of AQP4, loop A, C, and E were determined, a linker region was added. Then, the amino acid sequences were converted to nucleotide sequences, which was successfully nserted into an IRES vector.

Free Research Field

神経免疫

Academic Significance and Societal Importance of the Research Achievements

この成功により、AQP4の細胞外領域とIgG1 Fc領域の融合タンパク質（AQP4loopX-Fc）が抗AQP4抗体の中和と抗AQP4抗体産生B細胞に対する抗体介在性細胞傷害により、視神経脊髄炎を改善させることができるという作業仮説を証明する重要な一歩を踏み出すことができた。作業仮説が証明されれば、他の自己抗体関連神経免疫疾患のみならず、自己抗体の関連する数多くの病気の治療に応用できる可能性を秘める方法であり、学術的、社会的意義は小さくはないと考える。