An anti-TNF--α antibody mimetic to treat ocular inflammation

Article

Khalili, H., Lee, Richard W., Khaw, Peng Tee, Brocchini, Steve, Dick, Andrew D. and Copland, David A. 2016. An anti-TNF--α antibody mimetic to treat ocular inflammation. Scientific Reports. 6 (36905). https://doi.org/10.1038/srep36905

Publication dates
Authors	Khalili, H., Lee, Richard W., Khaw, Peng Tee, Brocchini, Steve, Dick, Andrew D. and Copland, David A.
Abstract	Infliximab is an antibody that neutralizes TNF-α and is used principally by systemic administration to treat many inflammatory disorders. We prepared the antibody mimetic Fab-PEG-Fab (FpFinfliximab) for direct intravitreal injection to assess whether such formulations have biological activity and potential utility for ocular use. FpFinfliximab was designed to address side effects caused by antibody degradation and the presence of the Fc region. Surface plasmon resonance analysis indicated that infliximab and FpFinfliximab maintained binding affinity for both human and murine recombinant TNF-α. No Fc mediated RPE cellular uptake was observed for FpFinfliximab. Both Infliximab and FpFinfliximab suppressed ocular inflammation by reducing the number of CD45+ infiltrate cells in the EAU mice model after a single intravitreal injection at the onset of peak disease. These results offer an opportunity to develop and formulate for ocular use, FpF molecules designed for single and potentially multiple targets using bi-specific FpFs.
Journal	Scientific Reports
Journal citation	6 (36905)
ISSN	2045-2322
	2045-2322
Year	2016
Publisher	Nature Publishing Group
Accepted author manuscript	SREP-16-26783 revised manuscript.pdf License CC BY
Publisher's version	srep36905.pdf License CC BY
Supplemental file	srep36905-s1.pdf License CC BY
Digital Object Identifier (DOI)	https://doi.org/10.1038/srep36905
Print	22 Nov 2016
Publication process dates
Deposited	21 Oct 2016
Accepted	20 Oct 2016
Funder	National Eye Research Centre
	UCL School of Pharmacy Research Innovation Fund
	National Institute of Health Research Biomedical Research Centre
	Moorfields Special Trustees
	Helen Hamlyn Trust
	Medical Research Council
	Fight For Sight
	Freemasons Grand Charity

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Accepted author manuscript

	SREP-16-26783 revised manuscript.pdf
License: CC BY

Publisher's version

	srep36905.pdf
License: CC BY

Supplemental file

	srep36905-s1.pdf
License: CC BY

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