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N Biotechnol. 2017 Oct 25;39(Pt B):167-173. doi: 10.1016/j.nbt.2016.12.010. Epub 2017 Jan 27.

Engineering bispecific antibodies with defined chain pairing.

Author information

1
Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Alarich-Weiss-Strasse 4, D-64287 Darmstadt, Germany; Protein Engineering and Antibody Technologies, Merck KGaA, Frankfurter Strasse 250, D-64293 Darmstadt, Germany.
2
Protein Engineering and Antibody Technologies, Merck KGaA, Frankfurter Strasse 250, D-64293 Darmstadt, Germany.
3
Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Alarich-Weiss-Strasse 4, D-64287 Darmstadt, Germany. Electronic address: Kolmar@Biochemie-TUD.de.
4
Protein Engineering and Antibody Technologies, Merck KGaA, Frankfurter Strasse 250, D-64293 Darmstadt, Germany. Electronic address: Stefan.c.Becker@merckgroup.com.

Abstract

Bispecific IgG-like antibodies can simultaneously interact with two epitopes on the same or on different antigens. Therefore, these molecules facilitate novel modes of action, which cannot be addressed by conventional monospecific IgGs. However, the generation of such antibodies still appears to be demanding due to their specific architecture comprising four different polypeptide chains that need to assemble correctly. This review focusses on different strategies to circumvent this issue or to enforce a correct chain association with a focus on common-chain bispecific antibodies.

KEYWORDS:

Antibody; Bispecific antibody; Common chain bispecific antibodies in clinical development; Common heavy chain; Common light chain; Ensuring cognate light chain pairing; Heavy chain heterodimerization

PMID:
28137467
DOI:
10.1016/j.nbt.2016.12.010
[Indexed for MEDLINE]

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