Scientific Reports · 2016 · 27 citations · 37 references
PharmacyImmunologyPharmacologyInflammationMonoclonal AntibodiesOcular ImmunologyAntibody CharacterizationAntibody FormulationOcular InflammationOcular Targeted DeliveryTherapeutic Antibody DevelopmentTherapeutic Monoclonal AntibodiesAnti-inflammatory Ocular Drug EffectsAnti-inflammatory Ocular TherapyAntibody Fc Fusion ProteinsFab Antibody FragmentsMediators Of Ocular InflammationSurface Plasmon Resonance AnalysisSystemic AdministrationTherapeutic Antibody Fc Design
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 (FpF infliximab ) for direct intravitreal injection to assess whether such formulations have biological activity and potential utility for ocular use. FpF infliximab 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 FpF infliximab maintained binding affinity for both human and murine recombinant TNF-α. No Fc mediated RPE cellular uptake was observed for FpF infliximab . Both Infliximab and FpF infliximab 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.
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Aqueous Humor and Serum Tumor Necrosis Factor-α in Clinical Uveitis
Manuel Santos Lacomba, Carmen Marcos Martín, J.M. Gallardo Galera et al. · Ophthalmic Research · 2001 · 295 citations
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