Fc receptor-targeted therapies for the treatment of inflammation, cancer and beyond

Hogarth, P. Mark; Pietersz, Geoffrey A.

doi:10.1038/nrd2909

Cited by 310 publications

(383 citation statements)

References 167 publications

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“…With repeated in vitro activation as high as a Ϸ50% cells demonstrate IC binding. Our result along with these previous studies are in contrast to several recent reports that argue for the lack of expression of FcRs on CD4 ϩ T lymphocytes (4,5,7,9,10,48). We believe that the lack of good antibodies against human FcRs and lack of proper reagents to analyze the expression of Fc␥RIII on activated CD4…”

Section: Discussioncontrasting

confidence: 55%

“…These studies suggest a role for FcR-␥ chain in T-cell physiology. Contrary to these reports, several reviews, including some recent, have emphasized the absence of FcRs on CD4 ϩ T lymphocytes (4,9,10). Establishing the presence and the conditions under which Fc␥RIIIa appears in CD4 ϩ T-cells is important for understanding the role these receptors can play in T-cell-mediated pathological events.…”

Section: ؉ Helper T-cells Is An Important Finding Since These Receptomentioning

confidence: 91%

“…Elevated levels of ICs are present in multiple disease conditions and contribute to the disease pathology by engaging Fc␥RIIIa on multiple cell types. These receptors are also targets for therapeutic interventions (9,10). For example, FcRs are implicated in the anti-inflammatory response observed with intravenous immunoglobulin (IVIG) therapy (11,12).…”

Section: ؉ Helper T-cells Is An Important Finding Since These Receptomentioning

confidence: 99%

See 2 more Smart Citations

Induced Expression of FcγRIIIa (CD16a) on CD4+ T Cells Triggers Generation of IFN-γhigh Subset

Chauhan

Chen

Moore

et al. 2015

Journal of Biological Chemistry

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Section: Discussioncontrasting

confidence: 55%

Section: ؉ Helper T-cells Is An Important Finding Since These Receptomentioning

confidence: 91%

Section: ؉ Helper T-cells Is An Important Finding Since These Receptomentioning

confidence: 99%

See 1 more Smart Citation

Induced Expression of FcγRIIIa (CD16a) on CD4+ T Cells Triggers Generation of IFN-γhigh Subset

Chauhan

Chen

Moore

et al. 2015

Journal of Biological Chemistry

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“…Interactions of IgGs with effector cells through fragment crystallizable γ (Fcγ) receptors are often considered a mode of action of therapeutic antibodies 2, 3, 4. Fcγ receptors are cell surface receptors that can be found on innate immune effector cells such as natural killer cells and macrophages.…”

mentioning

confidence: 99%

Rapid screening of IgG quality attributes – effects on Fc receptor binding

Geuijen¹,

Oppers-Tiemissen

Egging

et al. 2017

FEBS Open Bio

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The interactions of therapeutic antibodies with fragment crystallizable γ (Fcγ) receptors and neonatal Fc receptors (FcRn) are measured in vitro as indicators of antibody functional performance. Antibodies are anchored to immune cells through the Fc tail, and these interactions are important for the efficacy and safety of therapeutic antibodies. High‐throughput binding studies on each of the human Fcγ receptor classes (FcγRI, FcγRIIa, FcγRIIb, FcγRIIIa, and FcγRIIIb) as well as FcRn have been developed and performed with human IgG after stress‐induced modifications to identify potential impact in vivo. Interestingly, we found that asparagine deamidation (D‐N) reduced the binding of IgG to the low‐affinity Fcγ receptors (FcγRIIa, FcγRIIb, FcγRIIIa, and FcγRIIIb), while FcγRI and FcRn binding was not impacted. Deglycosylation completely inhibited binding to all Fcγ receptors, but showed no impact on binding to FcRn. On the other hand, afucosylation only impacted binding to FcγRIIIa and FcγRIIIb. Methionine oxidation at levels below 7%, multiple freeze/thaw cycles and short‐term thermal/shake stress did not influence binding to any of the Fc receptors. The presence of high molecular weight species, or aggregates, disturbed measurements in these binding assays; up to 5% of aggregates in IgG samples changed the binding and kinetics to each of the Fc receptors. Overall, the screening assays described in this manuscript prove that rapid and multiplexed binding assays may be a valuable tool for lead optimization, process development, in‐process controls, and biosimilarity assessment of IgGs during development and manufacturing of therapeutic IgGs.

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“…6 Biological responses induced via the Fc portions of antibodies are powerful and unusual, which can be exploited via the engineering of therapeutic monoclonal antibodies to improve their activity in vivo. 7 In fact, the modification of Fc receptor-mediated activities is emerging as one of the most promising ways to increase the clinical potential of antibodies. 1 Consequently, investigating the Fc receptor-mediated cellular cytotoxicity activity is of great significance for developing new antibodies with enhanced efficacies, which can then be used to improve the quality of life of patients.…”

Section: Introductionmentioning

confidence: 99%

Nanoscale Imaging and Mechanical Analysis of Fc Receptor-Mediated Macrophage Phagocytosis against Cancer Cells

Liu

et al. 2014

Langmuir

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Fc receptor-mediated macrophage phagocytosis against cancer cells is an important mechanism in the immune therapy of cancers. Traditional research about macrophage phagocytosis was based on optical microscopy, which cannot reveal detailed information because of the 200-nm-resolution limit. Quantitatively investigating the macrophage phagocytosis at micro-and nanoscale levels is still scarce. The advent of atomic force microscopy (AFM) offers an excellent analytical instrument for quantitatively investigating the biological processes at single-cell and singlemolecule levels under native conditions. In this work, we combined AFM and fluorescence microscopy to visualize and quantify the detailed changes in cell morphology and mechanical properties during the process of Fc receptor-mediated macrophage phagocytosis against cancer cells. Lymphoma cells were discernible by fluorescence staining. Then, the dynamic process of phagocytosis was observed by time-lapse optical microscopy. Next, AFM was applied to investigate the detailed cellular behaviors during macrophage phagocytosis under the guidance of fluorescence recognition. AFM imaging revealed the distinct features in cellular ultramicrostructures for the different steps of macrophage phagocytosis. AFM cell mechanical property measurements indicated that the binding of cancer cells to macrophages could make macrophages become stiffer. The experimental results provide novel insights in understanding the Fc-receptor-mediated macrophage phagocytosis.

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Fc receptor-targeted therapies for the treatment of inflammation, cancer and beyond

Cited by 310 publications

References 167 publications

Induced Expression of FcγRIIIa (CD16a) on CD4+ T Cells Triggers Generation of IFN-γhigh Subset

Induced Expression of FcγRIIIa (CD16a) on CD4+ T Cells Triggers Generation of IFN-γhigh Subset

Rapid screening of IgG quality attributes – effects on Fc receptor binding

Nanoscale Imaging and Mechanical Analysis of Fc Receptor-Mediated Macrophage Phagocytosis against Cancer Cells

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