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Fc-engineering for modulated effector functions—improving antibodies for cancer treatment

Fc-engineering for modulated effector functions—improving antibodies for cancer treatment
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 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.
Cragg, Mark
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Oldham, Robert James
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Teal, Emma Louise
cd1bd776-9311-4087-819e-ff2c25f793c4
Beers, Stephen
a02548be-3ffd-41ab-9db8-d6e8c3b499a2
Cragg, Mark
ec97f80e-f3c8-49b7-a960-20dff648b78c
Oldham, Robert James
844b9bff-16f0-4577-abba-b35afd02b923
Teal, Emma Louise
cd1bd776-9311-4087-819e-ff2c25f793c4
Beers, Stephen
a02548be-3ffd-41ab-9db8-d6e8c3b499a2

Cragg, Mark, Oldham, Robert James, Teal, Emma Louise and Beers, Stephen (2020) Fc-engineering for modulated effector functions—improving antibodies for cancer treatment. Antibodies, 9 (4). (doi:10.3390/antib9040064).

Record type: Article

Abstract

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.

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antibodies-09-00064 - Version of Record
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Accepted/In Press date: 4 November 2020
e-pub ahead of print date: 17 November 2020

Identifiers

Local EPrints ID: 445931
URI: http://eprints.soton.ac.uk/id/eprint/445931
PURE UUID: afd01c3f-8da0-4ccc-af85-a3de7219b8d8
ORCID for Mark Cragg: ORCID iD orcid.org/0000-0003-2077-089X
ORCID for Robert James Oldham: ORCID iD orcid.org/0000-0002-8007-1145
ORCID for Stephen Beers: ORCID iD orcid.org/0000-0002-3765-3342

Catalogue record

Date deposited: 14 Jan 2021 19:14
Last modified: 18 Feb 2021 17:30

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Contributors

Author: Mark Cragg ORCID iD
Author: Robert James Oldham ORCID iD
Author: Emma Louise Teal
Author: Stephen Beers ORCID iD

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