Development of transportable scFV monoclonal antibody into nucleus

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19387
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: Saitama Medical University
• Principal Investigator: Yamada Taketo 埼玉医科大学, 医学部, 教授 (60230463)
• Co-Investigator(Kenkyū-buntansha): 林 睦 慶應義塾大学, 医学部(信濃町), 助教 (60327575) ; 山田 幸司 東京慈恵会医科大学, 医学部, 准教授 (90570979)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: モノクローナル抗体 / 核内移行 / single chain Fv / がん細胞 / 免疫担当細胞

Outline of Final Research Achievements

Monoclonal antibodies (MoAbs) are promising biopharmaceuticals, however there was no technology to translocate MoAbs into the nucleus. We therefore analyzed the nuclear translocation of MoAbs in cancer cells by searching for antigens that translocate from the cell membrane to the nucleus and generating MoAbs. Using a MoAb panel and scFV library against cell membrane surface antigens, we analyzed the coexistence of nuclear localized molecules and antigens in the nucleus after MoAb treatment and selected cell membrane surface antigens that translocate into the nucleus. After immunizing mice with the purified candidate antigens, we created a fluorescent molecule-added library and selected clones to obtain fluorescent clones that interact with antigens and antibodies in the nucleus. As a result, it was revealed that the 13B1 antibody exhibits nuclear translocation in cancer cells specifically in vitro.

Free Research Field

分子病理学

Academic Significance and Societal Importance of the Research Achievements

モノクローナル抗体(MoAb)はバイオ医薬品の中で有望であり、抗体-薬剤複合体(Antibody-Drug Conjugate;ADC)や二重特異性抗体へ発展を遂げている。しかし、これまでMoAb自体を核内に移行させる技術はなかった。MoAbを核内まで輸送させることができれば、ADC化や二重特異性抗体化により、これまで不可能であった核内への機能抗体/分子の核移行による核酸合成阻害や修復修飾、エンハンサー機能の修飾による転写調節、核輸送の促進・阻害などが可能となり、抗体治療の画期的技術革新になりうると考える。