Boron Drug Development to Expand the Indication of Boron Neutron Capture Therapy to Refractory Non-neoplastic Diseases

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15805
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Kyoto University
• Principal Investigator: Watanabe Tsubasa 京都大学, 複合原子力科学研究所, 特定准教授 (30804348)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: ホウ素中性子捕捉療法

Outline of Final Research Achievements

Approximately 3.8 modules could be bound per antibody molecule (approximately 46 boron atoms per antibody molecule). For proof of concept, we first targeted CD8+ T cells, which can be easily extracted, and isolated CD8+ T cells from mouse spleens. The expression of CD8a protein in CD8+ T cells is 90,000, which is less than the amount of normal protein, and a theoretical 3% probability of boron neutron capture reaction occurs. The apoptosis after neutron irradiation was evaluated using flow cytometer RNA measurement, and an average increase of 2.8% of apoptotic cells was observed, which was almost consistent with the theoretical value.

Free Research Field

放射線腫瘍学・放射線生物学

Academic Significance and Societal Importance of the Research Achievements

既報のホウ素化抗体は、結合させられるホウ素クラスターの量が少なかったが、今回我々が開発したホウ素化モジュールによる抗体のホウ素化により抗体の抗原認識を損ねることなくより多くのホウ素原子を抗体に結合させることができた。ホウ素中性子捕捉療法は現在アミノ酸誘導体を主体としたホウ素薬剤のみが臨床応用可能であるが、抗体を用いた任意の細胞に対するホウ素原子の送達が可能となれば、ホウ素中性子捕捉療法の対象疾患を拡大することができる。今後、本モジュールのさらなる改良を目指し、より多くのホウ素原子を薬物送達の担体となる抗体へ結合させ、臨床応用の可能性を検討する。