Complement is a core component of the immune system, which performs vital roles in immune surveillance. However, the active products that enable complement to perform its physiological roles can inappropriately target self tissues and cause pathology. Complement-mediated inflammation and tissue destruction is an important drive to pathology in diseases as diverse as rheumatoid arthritis and dementia. Two decades ago there were no agents that could be used therapeutically to inhibit the activation of complement, but increased understanding of the natural control of complement in vivo has markedly changed this situation. The realization that drugs mimicking the action of the complement regulatory proteins present on self cells, and in plasma, could effectively control pathological activation of complement has opened the door to the use of anti-complement therapy in disease. Here we will review the development of anticomplement therapeutics from the first generation agents, which are unmodified recombinant forms of natural regulators, to recent strategies for making better drugs. We will describe strategies for targeting the anticomplement activity to the site of disease, and for extending the plasma half-life of the agent. Finally, we will illustrate a novel approach to the delivery of anticomplement agents, making prodrugs that are activated only at disease sites thus minimizing the deleterious effects of systemic complement inhibition.
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Conference Article|
November 01 2002
Tailoring anti-complement therapeutics
C. L. Harris;
C. L. Harris
1
1Complement Biology Group, Department of Medical Biochemistry, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, U.K.
1To whom correspondence should be addressed (e-mail harriscl@cardiff.ac.uk)
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D. A. Fraser;
D. A. Fraser
1Complement Biology Group, Department of Medical Biochemistry, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, U.K.
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B. P. Morgan
B. P. Morgan
1Complement Biology Group, Department of Medical Biochemistry, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, U.K.
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Publisher: Portland Press Ltd
Received:
June 18 2002
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2002 Biochemical Society
2002
Biochem Soc Trans (2002) 30 (6): 1019–1026.
Article history
Received:
June 18 2002
Citation
C. L. Harris, D. A. Fraser, B. P. Morgan; Tailoring anti-complement therapeutics. Biochem Soc Trans 1 November 2002; 30 (6): 1019–1026. doi: https://doi.org/10.1042/bst0301019
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