title: An anti-TNF-α antibody mimetic to treat ocular inflammation.
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. FpFinfliximabwas designed to address side effects caused by antibody degradation and the presence of the Fc region. Surface plasmon resonance analysis indicated that infliximab and FpFinfliximabmaintained binding affinity for both human and murine recombinant TNF-α. No Fc mediated RPE cellular uptake was observed for FpFinfliximab. Both Infliximab and FpFinfliximabsuppressed 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.
authors.affiliation: UCL School of Pharmacy, London, UK.|National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.|University of East London, School of Health, Sport and Bioscience, Water lane, Stratford campus, London, E15 4LZ, UK.
authors.forename: Hanieh
authors.initials: H
authors.lastname: Khalili
authors.affiliation: National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.|School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Lee
authors.affiliation: National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
authors.forename: Peng T
authors.initials: PT
authors.lastname: Khaw
authors.affiliation: UCL School of Pharmacy, London, UK.|National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
authors.forename: Steve
authors.initials: S
authors.lastname: Brocchini
authors.affiliation: National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.|School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Dick
authors.affiliation: National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.|School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Copland
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D000937:Antigen-Antibody Reactions; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000473:pathology; D004195:Disease Models, Animal; D005128:Eye Diseases / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D007249:Inflammation / Q000517:prevention & control*; D000069285:Infliximab / Q000737:chemistry / Q000276:immunology; D058449:Intravitreal Injections; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry; D020349:Surface Plasmon Resonance; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; D000069285:Infliximab; D017493:Leukocyte Common Antigens