Novel tetravalent and bispecific IgG-like antibody molecules combining single-chain diabodies with the immunoglobulin gamma l Fc or CH3 region

Citation
M. Alt et al., Novel tetravalent and bispecific IgG-like antibody molecules combining single-chain diabodies with the immunoglobulin gamma l Fc or CH3 region, FEBS LETTER, 454(1-2), 1999, pp. 90-94
Citations number
32
Categorie Soggetti
Biochemistry & Biophysics
Journal title
FEBS LETTERS
ISSN journal
00145793 → ACNP
Volume
454
Issue
1-2
Year of publication
1999
Pages
90 - 94
Database
ISI
SICI code
0014-5793(19990702)454:1-2<90:NTABIA>2.0.ZU;2-A
Abstract
Although bispecific IgG molecules have been successfully applied for antibo dy-mediated immunotherapy of tumours, applicability is hampered by the diff iculties associated with their generation. In the present study, me have us ed a bispecific single-chain diabody (scDb) directed against carcinoembryon ic antigen and Escherichia coli beta-galactosidase as a model to generate b ispecific IgG-like antibody molecules. We show that the fusion of this sing le-chain diabody to the Fc (scDb-Fc) or CH3 (scDb-CH3) region of the human immunoglobulin gamma 1 chain results in the expression of dimeric fusion pr oteins exhibiting four functional antigen binding sites with increased func tional affinity, This strategy represents a new and convenient way to gener ate IgG-like multivalent and bispecific molecules that are efficiently secr eted from mammalian cells. (C) 1999 Federation of European Biochemical Soci eties.