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Engineering IgG-Like Bispecific Antibodies—An Overview

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 complem...

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Autores principales: Krah, Simon, Kolmar, Harald, Becker, Stefan, Zielonka, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6640676/
https://www.ncbi.nlm.nih.gov/pubmed/31544880
http://dx.doi.org/10.3390/antib7030028
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author Krah, Simon
Kolmar, Harald
Becker, Stefan
Zielonka, Stefan
author_facet Krah, Simon
Kolmar, Harald
Becker, Stefan
Zielonka, Stefan
author_sort Krah, Simon
collection PubMed
description 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.
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spelling pubmed-66406762019-09-05 Engineering IgG-Like Bispecific Antibodies—An Overview Krah, Simon Kolmar, Harald Becker, Stefan Zielonka, Stefan Antibodies (Basel) Review 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. MDPI 2018-08-01 /pmc/articles/PMC6640676/ /pubmed/31544880 http://dx.doi.org/10.3390/antib7030028 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Krah, Simon
Kolmar, Harald
Becker, Stefan
Zielonka, Stefan
Engineering IgG-Like Bispecific Antibodies—An Overview
title Engineering IgG-Like Bispecific Antibodies—An Overview
title_full Engineering IgG-Like Bispecific Antibodies—An Overview
title_fullStr Engineering IgG-Like Bispecific Antibodies—An Overview
title_full_unstemmed Engineering IgG-Like Bispecific Antibodies—An Overview
title_short Engineering IgG-Like Bispecific Antibodies—An Overview
title_sort engineering igg-like bispecific antibodies—an overview
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6640676/
https://www.ncbi.nlm.nih.gov/pubmed/31544880
http://dx.doi.org/10.3390/antib7030028
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