Polymeric human Fc-fusion proteins with modified effector functions.

Scientific Reports
David N A MekhaielRichard J Pleass

Abstract

The success of Fc-fusion bio-therapeutics has spurred the development of other Fc-fusion products for treating and/or vaccinating against a range of diseases. We describe a method to modulate their function by converting them into well-defined stable polymers. This strategy resulted in cylindrical hexameric structures revealed by tapping mode atomic force microscopy (AFM). Polymeric Fc-fusions were significantly less immunogenic than their dimeric or monomeric counterparts, a result partly owing to their reduced ability to interact with critical Fc-receptors. However, in the absence of the fusion partner, polymeric IgG1-Fc molecules were capable of binding selectively to FcγRs, with significantly increased affinity owing to their increased valency, suggesting that these reagents may prove of immediate utility in the development of well-defined replacements for intravenous immunoglobulin (IVIG) therapy. Overall, these findings establish an effective IgG Fc-fusion based polymeric platform with which the therapeutic and vaccination applications of Fc-fusion immune-complexes can now be explored.

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Citations

Jul 28, 2012·EMBO Molecular Medicine·Daniel M CzajkowskyRichard J Pleass
Feb 3, 2016·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Arman MosavatSeyed Abdolrahim Rezaee
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Apr 29, 2015·Scientific Reports·Daniel M CzajkowskyRichard J Pleass
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Jan 27, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Patricia A BlundellRichard J Pleass
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Jan 8, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Patricia A BlundellRichard J Pleass
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Mar 12, 2021·Biochemical Society Transactions·Roberto DoniniCleo Kontoravdi

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Methods Mentioned

BETA
size-exclusion chromatography
AFM
FACS
ELISA
transgenic
PCR
enzyme-linked immunosorbent assay
affinity
gel filtration
chips

Software Mentioned

CELLQuest
PdbViewer
FlowJo
VMD
Swiss
BIAevaluation

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