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).
AuthorsKhalili, 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.

JournalScientific Reports
Journal citation6 (36905)
ISSN2045-2322
2045-2322
Year2016
PublisherNature Publishing Group
Accepted author manuscript
License
CC BY
Publisher's version
License
CC BY
Supplemental file
License
CC BY
Digital Object Identifier (DOI)doi:10.1038/srep36905
Publication dates
Print22 Nov 2016
Publication process dates
Deposited21 Oct 2016
Accepted20 Oct 2016
FunderNational 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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