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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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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. |
format | Online Article Text |
id | pubmed-6640676 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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