Complement therapeutics in inflammatory diseases: promising drug candidates for C3-targeted intervention.
There is increasing appreciation that complement dysregulation lies at the heart of numerous immune-mediated and inflammatory disorders. Complement inhibitors are therefore being evaluated as new therapeutic options in various clinical translation programs and the first clinically approved complement-targeted drugs have profoundly impacted the management of certain complement-mediated diseases. Among the many members of the intricate protein network of complement, the central component C3 represents a 'hot-spot' for complement-targeted therapeutic intervention. C3 modulates both innate and adaptive immune responses and is linked to diverse immunomodulatory systems and biological processes that affect human pathophysiology. Compelling evidence from preclinical disease models has shown that C3 interception may offer multiple benefits over existing therapies or even reveal novel therapeutic avenues in disorders that are not commonly regarded as complement-driven, such as periodontal disease. Using the clinically developed compstatin family of C3 inhibitors and periodontitis as illustrative examples, this review highlights emerging therapeutic concepts and developments in the design of C3-targeted drug candidates as novel immunotherapeutics for oral and systemic inflammatory diseases.
Division of Biodiagnostic Sciences and Technologies, INRASTES, National Center for Scientific Research 'Demokritos', Aghia Paraskevi Attikis, Greece.
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Mastellos
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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Ricklin
Department of Preventive and Restorative Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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Hajishengallis
Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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Hajishengallis
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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Lambris
D000818:Animals; D003176:Complement C3 / Q000037:antagonists & inhibitors* / Q000276:immunology; D051056:Complement Inactivating Agents / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology*; D058990:Molecular Targeted Therapy; D010518:Periodontitis / Q000188:drug therapy / Q000276:immunology
D003176:Complement C3; D051056:Complement Inactivating Agents
C3; complement; compstatin Cp40; inflammation, periodontitis; primate models; therapeutics