Fc-Engineering for Modulated Effector Functions—Improving Antibodies for Cancer Treatment
1
GlaxoSmithKline Research and Development, Stevenage SG1 2NY, UK
2
Antibody and Vaccine Group, Centre for Cancer Immunology, Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton SO171BJ, UK
3
Cancer Research UK Centre, Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton SO171BJ, UK
*
Author to whom correspondence should be addressed.
†
These authors contributed equally as lead authors.
Antibodies 2020, 9(4), 64; https://doi.org/10.3390/antib9040064
Received: 2 September 2020
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Revised: 28 September 2020
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Accepted: 4 November 2020
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Published: 17 November 2020
(This article belongs to the Special Issue Antibody Engineering for Cancer Immunotherapy)
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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Keywords:
Fc-engineering; Fc gamma receptor; antibody immunotherapy; complement; antibody-dependent cellular cytotoxicity (ADCC); antibody-dependent cellular phagocytosis (ADCP)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
MDPI and ACS Style
Liu, R.; Oldham, R.J.; Teal, E.; Beers, S.A.; Cragg, M.S. Fc-Engineering for Modulated Effector Functions—Improving Antibodies for Cancer Treatment. Antibodies 2020, 9, 64. https://doi.org/10.3390/antib9040064
AMA Style
Liu R, Oldham RJ, Teal E, Beers SA, Cragg MS. Fc-Engineering for Modulated Effector Functions—Improving Antibodies for Cancer Treatment. Antibodies. 2020; 9(4):64. https://doi.org/10.3390/antib9040064
Chicago/Turabian StyleLiu, Rena, Robert J. Oldham, Emma Teal, Stephen A. Beers, and Mark S. Cragg. 2020. "Fc-Engineering for Modulated Effector Functions—Improving Antibodies for Cancer Treatment" Antibodies 9, no. 4: 64. https://doi.org/10.3390/antib9040064
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