Novel tetravalent and bispecific IgG‐like antibody molecules combining single‐chain diabodies with the immunoglobulin γ1 Fc or CH3 region

FEBS Letters

Müller, Rolf¹  Kontermann, Roland E¹  Alt, Margitta¹ 

[1] Institut für Molekularbiologie und Tumorforschung, Philipps-Universität Marburg, Emil-Mannkopff-Straße 2, D-35033 Marburg, Germany

关键词: Single-chain diabody;    Bispecific antibody;    Immunoglobulin constant domain;    Dimerization;    Functional affinity;   

DOI  :  10.1016/S0014-5793(99)00782-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Although bispecific IgG molecules have been successfully applied for antibody-mediated immunotherapy of tumours, applicability is hampered by the difficulties associated with their generation. In the present study, we have used a bispecific single-chain diabody (scDb) directed against carcinoembryonic antigen and Escherichia coli β-galactosidase as a model to generate bispecific IgG-like antibody molecules. We show that the fusion of this single-chain diabody to the Fc (scDb-Fc) or CH3 (scDb-CH3) region of the human immunoglobulin γ1 chain results in the expression of dimeric fusion proteins exhibiting four functional antigen binding sites with increased functional affinity. This strategy represents a new and convenient way to generate IgG-like multivalent and bispecific molecules that are efficiently secreted from mammalian cells.

【 授权许可】

Unknown