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