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Engineering IgG-Like Bispecific Antibodies — An Overview

Krah, Simon ; Kolmar, Harald ; Becker, Stefan ; Zielonka, Stefan (2024)
Engineering IgG-Like Bispecific Antibodies — An Overview.
In: Antibodies, 2018, 7 (3)
doi: 10.26083/tuprints-00015758
Article, Secondary publication, Publisher's Version

Copyright Information: CC BY 4.0 International - Creative Commons, Attribution.

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Item Type: Article
Type of entry: Secondary publication
Title: Engineering IgG-Like Bispecific Antibodies — An Overview
Language: English
Date: 16 January 2024
Place of Publication: Darmstadt
Year of primary publication: 2018
Place of primary publication: Basel
Publisher: MDPI
Journal or Publication Title: Antibodies
Volume of the journal: 7
Issue Number: 3
Collation: 10 Seiten
DOI: 10.26083/tuprints-00015758
Corresponding Links:
Origin: Secondary publication DeepGreen

Monoclonal antibody therapeutics have proven to be successful treatment options for patients in 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.

Uncontrolled Keywords: bispecific antibodies, cognate light chain pairing, common heavy chain, common light chain, heavy chain heterodimerization, knobs into holes, SEED
Status: Publisher's Version
URN: urn:nbn:de:tuda-tuprints-157585
Additional Information:

This article belongs to the Special Issue Bispecific Antibodies-Opportunities and Challenges

Classification DDC: 500 Science and mathematics > 540 Chemistry
500 Science and mathematics > 570 Life sciences, biology
Divisions: 07 Department of Chemistry > Clemens-Schöpf-Institut > Fachgebiet Biochemie
Date Deposited: 16 Jan 2024 12:34
Last Modified: 18 Jan 2024 10:22
SWORD Depositor: Deep Green
URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/15758
PPN: 514765801
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