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Fc-Engineering for Modulated Effector Functions—Improving Antibodies for Cancer Treatment
The majority of monoclonal antibody (mAb) therapeutics possess the ability to engage innate immune effectors through interactions mediated by their fragment crystallizable (Fc) domain. By delivering Fc-Fc gamma receptor (FcγR) and Fc-C1q interactions, mAb are able to link exquisite specificity to po...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709126/ https://www.ncbi.nlm.nih.gov/pubmed/33212886 http://dx.doi.org/10.3390/antib9040064 |
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author | Liu, Rena Oldham, Robert J. Teal, Emma Beers, Stephen A. Cragg, Mark S. |
author_facet | Liu, Rena Oldham, Robert J. Teal, Emma Beers, Stephen A. Cragg, Mark S. |
author_sort | Liu, Rena |
collection | PubMed |
description | The majority of monoclonal antibody (mAb) therapeutics possess the ability to engage innate immune effectors through interactions mediated by their fragment crystallizable (Fc) domain. By delivering Fc-Fc gamma receptor (FcγR) and Fc-C1q interactions, mAb are able to link exquisite specificity to powerful cellular and complement-mediated effector functions. Fc interactions can also facilitate enhanced target clustering to evoke potent receptor signaling. These observations have driven decades-long research to delineate the properties within the Fc that elicit these various activities, identifying key amino acid residues and elucidating the important role of glycosylation. They have also fostered a growing interest in Fc-engineering whereby this knowledge is exploited to modulate Fc effector function to suit specific mechanisms of action and therapeutic purposes. In this review, we document the insight that has been generated through the study of the Fc domain; revealing the underpinning structure-function relationships and how the Fc has been engineered to produce an increasing number of antibodies that are appearing in the clinic with augmented abilities to treat cancer. |
format | Online Article Text |
id | pubmed-7709126 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77091262020-12-03 Fc-Engineering for Modulated Effector Functions—Improving Antibodies for Cancer Treatment Liu, Rena Oldham, Robert J. Teal, Emma Beers, Stephen A. Cragg, Mark S. Antibodies (Basel) Review The majority of monoclonal antibody (mAb) therapeutics possess the ability to engage innate immune effectors through interactions mediated by their fragment crystallizable (Fc) domain. By delivering Fc-Fc gamma receptor (FcγR) and Fc-C1q interactions, mAb are able to link exquisite specificity to powerful cellular and complement-mediated effector functions. Fc interactions can also facilitate enhanced target clustering to evoke potent receptor signaling. These observations have driven decades-long research to delineate the properties within the Fc that elicit these various activities, identifying key amino acid residues and elucidating the important role of glycosylation. They have also fostered a growing interest in Fc-engineering whereby this knowledge is exploited to modulate Fc effector function to suit specific mechanisms of action and therapeutic purposes. In this review, we document the insight that has been generated through the study of the Fc domain; revealing the underpinning structure-function relationships and how the Fc has been engineered to produce an increasing number of antibodies that are appearing in the clinic with augmented abilities to treat cancer. MDPI 2020-11-17 /pmc/articles/PMC7709126/ /pubmed/33212886 http://dx.doi.org/10.3390/antib9040064 Text en © 2020 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 Liu, Rena Oldham, Robert J. Teal, Emma Beers, Stephen A. Cragg, Mark S. Fc-Engineering for Modulated Effector Functions—Improving Antibodies for Cancer Treatment |
title | Fc-Engineering for Modulated Effector Functions—Improving Antibodies for Cancer Treatment |
title_full | Fc-Engineering for Modulated Effector Functions—Improving Antibodies for Cancer Treatment |
title_fullStr | Fc-Engineering for Modulated Effector Functions—Improving Antibodies for Cancer Treatment |
title_full_unstemmed | Fc-Engineering for Modulated Effector Functions—Improving Antibodies for Cancer Treatment |
title_short | Fc-Engineering for Modulated Effector Functions—Improving Antibodies for Cancer Treatment |
title_sort | fc-engineering for modulated effector functions—improving antibodies for cancer treatment |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709126/ https://www.ncbi.nlm.nih.gov/pubmed/33212886 http://dx.doi.org/10.3390/antib9040064 |
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