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Polymeric human Fc-fusion proteins with modified effector functions.

Mekhaiel, David, Czajkowsky, Daniel M, Andersen, Jan Terje, Shi, Jianguo, El-Faham, Marwa, Doenhoff, Michael, McIntosh, Richard S, Sandlie, Inger, He, Jianfeng, Hu, Jun, Shao, Zhifeng and Pleass, Richard ORCID: https://orcid.org/0000-0001-7438-8296 (2011) 'Polymeric human Fc-fusion proteins with modified effector functions.'. Scientific reports, Vol 1, p. 124.

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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.

Item Type: Article
Additional Information: Article is open access and can be found at the given URL.
Uncontrolled Keywords: Synthetic biology Immunology Biotechnology Nanobiotechnology
Subjects: W General Medicine. Health Professions > W 82 Biomedical technology (General)
QV Pharmacology > QV 34 Experimental pharmacology (General)
QW Microbiology and Immunology > QW 4 General works. Classify here works on microbiology as a whole.
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1038/srep00124
Depositing User: Mary Creegan
Date Deposited: 26 Feb 2013 10:48
Last Modified: 06 Feb 2018 13:05
URI: https://archive.lstmed.ac.uk/id/eprint/3230

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