Complement as New Immunotherapy Target

The complement system, an important component of innate immunity, functions as a first-line host defense in the prevention of microbial infections, clearance of immune complexes, and regulation of adaptive immunity. The complement system is tightly regulated by a number of cell membrane-bound and circulating regulatory proteins to prevent autologous tissue injury. Deregulated or excessive complement activation is now recognized as a key pathogenic driver in a wide spectrum of immune-mediated and inflammatory diseases, ranging from hematological and aging-related ocular pathologies to cancer, autoimmunity, oral diseases and neuroinflammatory, and neurodegenerative disorders. The first decade of clinical experience with complement-specific drug eculizumab (anti-human C5 antibody) has initiated a wave of complement inhibition therapeutics. Now more than 20 candidate drugs that target various stages of complement pathways are being evaluated in clinical trials. In this chapter, the physiological and pathophysiological associations of complement activation with the consequences for diseases are discussed and the approaches for current and next-generation therapeutics are summarized.