Complement and Immunotherapeutics

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About this Research Topic

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Background

The complement system is one of the major constituents of innate immunity, capable not only of killing microbes but also to perform opsonization and guidance of adaptive immunity as well as to scavenge cellular debris, thus limiting the risk of autoimmune events. For a long time the complement was considered a scientifically interesting system with limited physiological relevance. Such view dramatically changed during the last thirty years as direct or indirect involvement of the complement system has been reported in most human diseases. Practical therapeutic approaches employ either complement stimulation, for better eradication of microbes and tumor cells, or inhibition, in case of complement-driven autoimmune events. Recent insights on the role of complement in maintenance of body homeostasis, metabolism, mobilization of regulatory T cells, angiogenesis and interference with intracellular signaling, together with molecular insights of complement activation by antibodies, opened new avenues for effective complement-based immunotherapy.

Complement is considered as an effector mechanism of the first anticancer monoclonal antibody (rituximab) approved for clinical use more than 20 years ago. Since then, new generations of complement-activating drugs have been invented and dozens of candidates are now being tested in ongoing clinical trials. Reports on synergistic effects of complement modulators and immune checkpoint inhibitors give prospect for new therapeutic strategies in cancer therapy. First approved complement inhibitor eculizumab is highly efficient in treatment of atypical hemolytic uremic syndrome and paroxysmal nocturnal hemoglobinuria. Similarly C3, factor B and factor D inhibitors hold promise in blocking undesired complement activation in numerous pathogenic conditions. The fact that markers of complement activation are found in rheumatic, inflammatory, neurodegenerative and metabolic diseases underline the implications of complement in the pathogenesis of these disorders and opens the way for potential therapeutic intervention.

The aim of this Research Topic is to make readers familiar with new directions in complement-related immunotherapy. It is supposed to become a forum for announcing Original Articles and Reviews describing basic and translational studies, clinical reports as well as meta-analyses, connected to the modulation of the complement system for curing human diseases or the improvement of existing therapies. We welcome studies from the fields (but not limited to) of cancer, hematology, stroke, arthritis, ophthalmology, thrombosis, nephrology, transplantology and transfusion medicine, neurodegenerative and cutaneous disorders.

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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