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.
Sci Rep. 2016 Nov 22;6:36905. doi: 10.1038/srep36905.
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) for direct intravitreal injection to assess whether such formulations have biological activity and potential utility for ocular use. FpF 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 maintained binding affinity for both human and murine recombinant TNF-α. No Fc mediated RPE cellular uptake was observed for FpF. Both Infliximab and FpF 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.
英夫利昔单抗是一种中和 TNF-α 的抗体，主要通过全身给药用于治疗多种炎症性疾病。我们制备了抗体模拟 Fab-PEG-Fab（FpF）用于直接玻璃体内注射，以评估这些制剂是否具有生物活性和用于眼部应用的潜力。FpF 的设计旨在解决抗体降解和 Fc 区域存在引起的副作用。表面等离子体共振分析表明，英夫利昔单抗和 FpF 保持对人源和鼠源重组 TNF-α 的结合亲和力。未观察到 FpF 介导的 RPE 细胞摄取。在疾病高峰期开始时单次玻璃体内注射后，英夫利昔单抗和 FpF 均通过减少 EAU 小鼠中 CD45+浸润细胞的数量来抑制眼部炎症。这些结果为开发和配制用于眼部应用的 FpF 分子提供了机会，这些分子可使用双特异性 FpF 针对单一和潜在的多个靶标进行设计。
