Research Abstract

高い細胞傷害活性をもつ低分子型二重特異性抗体のセミハイスループットなスクリーニング手法 ブックマーク

A semi high-throughput method for screening small bispecific antibodies with high cytotoxicity

2017年6月6日 Scientific Reports 7 : 2862 doi: 10.1038/s41598-017-03101-4 (2017)


Aruto Sugiyama, Mitsuo Umetsu, Hikaru Nakazawa, Teppei Niide, Tomoko Onodera, Katsuhiro Hosokawa, Shuhei Hattori, Ryutaro Asano and Izumi Kumagai

Corresponding Authors

梅津 光央
東北大学大学院 工学研究科 バイオ工学専攻

熊谷 泉
東北大学大学院 工学研究科 バイオ工学専攻

Small bispecific antibodies that induce T-cell–mediated cytotoxicity have the potential to damage late-stage tumor masses to a clinically relevant degree, but their cytotoxicity is critically dependent on their structural and functional properties. Here, we constructed an optimized procedure for identifying highly cytotoxic antibodies from a variety of the T-cell–recruiting antibodies engineered from a series of antibodies against cancer antigens of epidermal growth factor receptor family and T-cell receptors. By developing and applying a set of rapid operations for expression vector construction and protein preparation, we screened the cytotoxicity of 104 small antibodies with diabody format and identified some with 103-times higher cytotoxicity than that of previously reported active diabody. The results demonstrate that cytotoxicity is enhanced by synergistic effects between the target, epitope, binding affinity, and the order of heavy-chain and light-chain variable domains. We demonstrate the importance of screening to determine the critical rules for highly cytotoxic antibodies.