Therapeutic monoclonal antibodies in ophthalmology.
Monoclonal antibodies (mAbs) can be used therapeutically by binding to molecular targets with high specificity. Therefore, they have excellent therapeutic applications in ophthalmology. This manuscript presents four aspects of the therapeutic use of mAbs in ophthalmology: the scientific rationale, the unique characteristics of selected mAbs, the current state-of-the-art application, and relevant therapeutic mAbs for future applications in ophthalmology. We identified in the literature various single-agent therapies that inhibit the following targets: tumor necrosis factor (TNF), epithelial growth factor receptor, vascular endothelial growth factor (VEGF) receptor, basic fibroblast growth factor receptor, platelet-derived growth factor, and cluster of differentiation antigens. The roles of all biochemical targets in ocular diseases were evaluated. Current and future mAbs against various cytokines were assessed for the treatment of ocular diseases. The medical literature showed the clinical benefits of mAbs for treating angiogenic and inflammatory ocular diseases. Two anti-VEGF mAbs, bevacizumab and ranibizumab, and three anti-TNF agents, infliximab, etanercept, and adalimumab, control ocular neovascularization and intraocular inflammation. Other mAbs such as rituximab, daclizumab, efalizumab, and alemtuzumab showed positive results in animal and early clinical studies and may represent useful adjuvant therapies for ocular lymphoma or ocular inflammation. Ranibizumab is the only FDA-approved therapy; for other mAbs the so-called off-label application remains the standard. Intravenous administration of mAbs has demonstrated acceptable toxicity profiles, while intraocular injection may decrease the chances of systemic complications and increase the amount of drug available to the retina and choroid. In conclusion, effective clinical use of mAbs in ophthalmology is more commonly seen in the field of angiogenic vitreoretinal and autoimmune inflammatory diseases. The challenge for the future is combining biologic therapies to improve the quality and duration of responses while diminishing side effects. The role of mAbs within ophthalmic treatments will be defined according to future clinical experience and the results of randomized clinical trials.
Rodrigues
Eduardo B
EB
Vision Institute, Department of Ophthalmology, Federal University of São Paulo, São Paulo, Brazil. edubrodriguess@yahoo.com.br
Farah
Michel E
ME
Maia
Maurício
M
Penha
Fernando M
FM
Regatieri
Caio
C
Melo
Gustavo B
GB
Pinheiro
Marcelo M
MM
Zanetti
Carlos R
CR
D000068879:Adalimumab; D000074323:Alemtuzumab; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D000068258:Bevacizumab; D000077561:Daclizumab; D000068800:Etanercept; D005128:Eye Diseases / Q000628:therapy*; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D009389:Neovascularization, Pathologic / Q000628:therapy*; D000069579:Ranibizumab; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000068258:Bevacizumab; D000074323:Alemtuzumab; D000069283:Rituximab; D000069285:Infliximab; D000077561:Daclizumab; D000068879:Adalimumab; D000068800:Etanercept; C472181:efalizumab; D000069579:Ranibizumab