eprintid: 1530804
rev_number: 34
eprint_status: archive
userid: 608
dir: disk0/01/53/08/04
datestamp: 2016-12-06 10:59:33
lastmod: 2021-09-19 23:53:53
status_changed: 2016-12-06 10:59:33
type: article
metadata_visibility: show
creators_name: Khalili, H
creators_name: Lee, RW
creators_name: Khaw, PT
creators_name: Brocchini, S
creators_name: Dick, AD
creators_name: Copland, DA
title: An anti-TNF-α antibody mimetic to treat ocular inflammation
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D08
divisions: C08
divisions: D10
divisions: G08
note: Copyright © The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/). The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.
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 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.
date: 2016-11-22
date_type: published
official_url: http://dx.doi.org/10.1038/srep36905
oa_status: green
full_text_type: pub
pmcid: PMC5118814
language: eng
primo: open
primo_central: open_green
article_type_text: Journal Article
verified: verified_manual
elements_id: 1194251
doi: 10.1038/srep36905
pii: srep36905
lyricists_name: Brocchini, Steve
lyricists_name: Dick, Andrew
lyricists_name: Khaw, Peggy
lyricists_name: Khaw, Peng Tee
lyricists_name: Lee, Richard
lyricists_id: SBROC55
lyricists_id: ADICK82
lyricists_id: PKHAW35
lyricists_id: PTKHA24
lyricists_id: RWJLE71
actors_name: Khaw, Peng Tee
actors_name: Dave, Sudershana
actors_id: PTKHA24
actors_id: DSUND42
actors_role: owner
actors_role: impersonator
full_text_status: public
publication: Scientific Reports
volume: 6
article_number: 36905
event_location: England
issn: 2045-2322
citation:        Khalili, H;    Lee, RW;    Khaw, PT;    Brocchini, S;    Dick, AD;    Copland, DA;      (2016)    An anti-TNF-α antibody mimetic to treat ocular inflammation.                   Scientific Reports , 6     , Article 36905.  10.1038/srep36905 <https://doi.org/10.1038/srep36905>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/1530804/1/Khalili_An%20anti-TNF%20antibody%20mimetic%20to%20treat%20ocular%20inflammation%20VoR.pdf
document_url: https://discovery.ucl.ac.uk/id/eprint/1530804/2/Khalili_An%20anti-TNF%20antibody%20mimetic%20to%20treat%20ocular%20inflammation%20Supplementary%20file.pdf