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Updated: Dec 1, 2025

Assessment of Human Natural Killer Cell Events Driven by FcγRIIIa Engagement in the Presence of Therapeutic Antibodies

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Published on: May 22, 2020

Fc γ receptor compositional heterogeneity: Considerations for immunotherapy development.

¹Department of Biochemistry and Molecular Biology, Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA.

The Journal of Biological Chemistry

|November 11, 2020

Summary

Fcγ receptors (FcγRs) are crucial for antibody-based therapies but poorly understood. This review details FcγR composition and engineering strategies to improve their function for enhanced immune-related disease treatments.

Keywords:

Fc receptor antibody glycobiology glycoprotein immunotherapy

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Area of Science:

Immunology
Molecular Biology
Therapeutic Antibody Engineering

Background:

Fcγ receptors (FcγRs) mediate cellular responses to antibody-bound targets, playing a key role in therapeutic monoclonal antibody (mAb) efficacy.
Despite their importance, FcγR development lags behind antibody engineering, hindering optimization of immune responses.
FcγRs exhibit significant heterogeneity due to genetic variations, isoforms, and post-translational modifications, complicating their study and engineering.

Purpose of the Study:

To review the composition of endogenous FcγRs found on human leukocytes.
To summarize recent advancements in engineering FcγRs for improved therapeutic applications.
To identify potential FcγR features that could enhance clinical function and accelerate development of new therapies.

Main Methods:

Analysis of FcγR composition from primary human leukocytes.
Review of current literature on FcγR engineering strategies.
Identification of key FcγR structural and functional elements for targeted modification.

Main Results:

FcγRs are highly heterogeneous, with diverse alleles, forms (membrane-tethered, soluble), and glycosylation patterns.
Engineered cell-based immunotherapies offer a platform for introducing modified FcγRs into clinical settings.
A fundamental lack of knowledge regarding endogenous FcγR forms limits current improvement efforts.

Conclusions:

Understanding the endogenous FcγR landscape is critical for rational engineering.
Targeted engineering of FcγRs holds promise for developing more effective immunotherapies.
Further research into FcγR biology can accelerate treatments for immune-related diseases.