Preferential heterodimerization of a bispecific diabody based on a humanized anti-EGFR antibody 528

被引：12

作者：

Asano, Ryutaro ^{[1
]}

Sone, Yukiko ^{[1
]}

Ikoma, Keiko ^{[1
]}

Hayashi, Hiroki ^{[2
]}

Nakanishi, Takeshi ^{[1
]}

Umetsu, Mitsuo ^{[1
]}

Katayose, Yu ^{[2
]}

Unno, Michiaki ^{[2
]}

Kudo, Toshio ^{[3
]}

Kumagai, Izumi ^{[1
]}

机构：

[1] Tohoku Univ, Grad Sch Engn, Dept Biomol Engn, Sendai, Miyagi 9808579, Japan

[2] Tohoku Univ, Grad Sch Med, Dept Surg, Div Gastroenterol Surg, Sendai, Miyagi 9808574, Japan

[3] Tohoku Univ, Inst Dev Aging & Canc, Cell Resource Ctr Biomed Res, Sendai, Miyagi 9808575, Japan

来源：

PROTEIN ENGINEERING DESIGN & SELECTION | 2008年 / 21卷 / 10期

基金：

日本学术振兴会;

关键词：

bispecific diabody; cancer immunotherapy; EGFR; in vitro refolding; small recombinant antibody;

D O I：

10.1093/protein/gzn037

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We report the utility of in vitro refolding in the preparation of monomorphous hEx3 bispecific diabodies with epidermal growth factor receptor and CD3 retargeting from insoluble aggregates in Escherichia coli. Appropriate interaction between cognate variable heavy and light chains led to the formation of functional hEx3 heterodimers in a diabody format rather than inactive homodimers. The refolded hEx3 was found to exhibit almost the equivalent activity to the hEx3 and single-chain hEx3 ( hEx3-scDb) prepared in a mammalian secretion system. We suggest that the preparation of hEx3 from bacterial insoluble material by means of in vitro refolding would be useful for industrial-scale production of the diabody for its potential use in clinical studies.

引用

页码：597 / 603

页数：7

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