The first constant domain (CH1 and CL) of an antibody used as heterodimerization domain for bispecific miniantibodies

被引：73

作者：

Müller, KM

Arndt, KM

Strittmatter, W

Plückthun, A

机构：

[1] Univ Zurich, Inst Biochem, CH-8057 Zurich, Switzerland

[2] Merck KGAA, D-64271 Darmstadt, Germany

来源：

FEBS LETTERS | 1998年 / 422卷 / 02期

关键词：

bispecific antibody; scFv fragment; tumor targeting; CD2; EGF receptor;

D O I：

10.1016/S0014-5793(98)00021-0

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：

Bispecific miniantibodies were constructed by genetically fusing the C(H)1 domain of an IgG1 to the C-terminus of a single-chain Fv fragment (scFv-425), specific for the EGF receptor, and fusing the CL domain of a kappa light chain to the C-terminus of a scFv specific for CD2 (scFv-M1). An efficient dicistronic gene arrangement for functional expression in Escherichia coli was constructed. Immunoblots demonstrated correct domain assembly and the formation of the natural C(H)1-C-L disulfide bridge. Gel filtration confirmed the correct size, sandwich ELISAs demonstrated bispecific functionality, and SPR biosensor measurements determined binding to EGF-R in comparison to bivalent constructs. Bispecific anti-EGF-R/anti-CD2 miniantibodies are candidates for the immunotherapy of cancer. (C) 1998 Federation of European Biochemical Societies.

引用

页码：259 / 264

页数：6

共 45 条

[1] DNA-SEQUENCE OF THE CONSTANT GENE REGION OF THE MOUSE IMMUNOGLOBULIN-KAPPA CHAIN [J].