Novel tetravalent and bispecific IgG‐like antibody molecules combining single‐chain diabodies with the immunoglobulin γ1 Fc or CH3 region
1999; Wiley; Volume: 454; Issue: 1-2 Linguagem: Inglês
10.1016/s0014-5793(99)00782-6
ISSN1873-3468
AutoresMargitta Alt, Rolf Müller, Roland E. Kontermann,
Tópico(s)Advanced Biosensing Techniques and Applications
ResumoAlthough 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.
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