MAPPs assay to elucidate the influences of the change of FcRn affinity on the antigen presentation.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06705
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: National Institute of Health Sciences
• Principal Investigator: Suzuki Takuo 国立医薬品食品衛生研究所, 生物薬品部, 主任研究官 (10415466)
• Co-Investigator(Kenkyū-buntansha): 橋井 則貴 国立医薬品食品衛生研究所, 生物薬品部, 室長 (20425672)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: FcRn / 抗体医薬品 / 抗原提示 / MAPPs

Outline of Final Research Achievements

Therapeutic immunoglobulin G (IgG) antibodies have comparatively long half-lives because the neonatal Fc receptor (FcRn) binds to the IgG Fc at acidic pH in the endosome and protects IgG from degradation. To prolong the half-lives of therapeutic IgG antibodies and thereby reduce the required dose and frequency, amino acid-substituted antibodies having high affinity to FcRn are being developed and some antibodies have been approved. On the other hand, since FcRn is also considered to play important role in transcytosis of IgGs and trafficking of antigen-bearing IgGs in antigen-presenting cells, the biodistribution and the antigen presentation may be affected by FcRn affinity. In this study, the antigen presentation of FcRn-binding engineered antibodies was analyzed using MHC-associated peptide proteomics (MAPPs) assay.

Free Research Field

バイオ医薬品評価科学

Academic Significance and Societal Importance of the Research Achievements

近年FcRn親和性の異なる抗体医薬品が承認されてきているものの、FcRn親和性改変抗体の抗原提示については、不明な点が多い。本研究はMHC-Associated Peptide Proteomicsの手法を用いてFcRn親和性改変抗体の抗原提示を分析する研究であり、これまでの研究を大きく推進させ、新たな知見が得られることが期待される。本研究により得られる成果は、今後の効果的な抗体医薬品類の分子設計につながると共に、FcRn親和性の異なる医薬品の有効性、安全性に関する知見として非常に重要な意味を持つ。