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Antibodies 2018, 7(3), 28; https://doi.org/10.3390/antib7030028

Engineering IgG-Like Bispecific Antibodies—An Overview

1
Protein Engineering and Antibody Technologies, Merck KGaA, Frankfurter Strasse 250, D-64293 Darmstadt, Germany
2
Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Alarich-Weiss-Strasse 4, D-64287 Darmstadt, Germany
*
Authors to whom correspondence should be addressed.
Received: 4 July 2018 / Revised: 24 July 2018 / Accepted: 24 July 2018 / Published: 1 August 2018
(This article belongs to the Special Issue Bispecific Antibodies-Opportunities and Challenges)
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Abstract

Monoclonal antibody therapeutics have proven to be successful treatment options for patients, which have various indications. Particularly in oncology, therapeutic concepts involving antibodies often rely on the so-called effector functions, such as antibody dependent cellular cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC), which are programed in the antibody Fc region. However, Fc-mediated effector mechanisms often seem to be insufficient in properly activating the immune system to act against tumor cells. Furthermore, long term treatments can lead to resistance against the applied drug, which is monospecific by nature. There is promise in using specific antibodies to overcome such issues due to their capability of recruiting and activating T-cells directly at the tumor site, for instance. During the last decade, two of these entities, which are referred to as Blinatumomab and Catumaxomab, have been approved to treat patients with acute lymphoblastic leukemia and malignant ascites. In addition, Emicizumab, which is a bispecific antibody targeting clotting factors IXa and X, was recently granted market approval by the FDA in 2017 for the treatment of hemophilia A. However, the generation of these next generation therapeutics is challenging and requires tremendous engineering efforts as two distinct paratopes need to be combined from two different heavy and light chains. This mini review summarizes technologies, which enable the generation of antibodies with dual specificities. View Full-Text
Keywords: bispecific antibodies; cognate light chain pairing; common heavy chain; common light chain; heavy chain heterodimerization; knobs into holes; SEED bispecific antibodies; cognate light chain pairing; common heavy chain; common light chain; heavy chain heterodimerization; knobs into holes; SEED
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Krah, S.; Kolmar, H.; Becker, S.; Zielonka, S. Engineering IgG-Like Bispecific Antibodies—An Overview. Antibodies 2018, 7, 28.

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