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Complement-targeted therapeutics

Nature Biotechnology volume 25, pages 1265–1275 (2007)Cite this article

Abstract

The complement system is a central component of innate immunity and bridges the innate to the adaptive immune response. However, it can also turn its destructive capabilities against host cells and is involved in numerous diseases and pathological conditions. Modulation of the complement system has been recognized as a promising strategy in drug discovery, and a large number of therapeutic modalities have been developed. However, successful marketing of complement-targeted drugs has proved to be more difficult than initially expected, and many strategies have been discontinued. The US Food and Drug Administration's approval of the first complement-specific drug, an antibody against complement component C5 (eculizumab; Soliris), in March 2007, was a long-awaited breakthrough in the field. Approval of eculizumab validates the complement system as therapeutic target and might facilitate clinical development of other promising drug candidates.

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Figure 1: The complement system as a bridge between innate and adaptive immunity.

Katie Ris-Vicari

Figure 2: Activation, regulation and therapeutic modulation of the complement system.
Figure 3: Examples of pathological conditions involving the complement system.

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Acknowledgements

We thank Peter Ward, Wenchao Song and Maciej Markiewski for their input and for critically reading the manuscript and Deborah McClellan for editorial assistance. This work was supported by National Institutes of Health grants GM-069736, GM-62134, AI-30040, EB003968, CA112162 and AI-068730.

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  1. Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, 401 Stellar Chance, 422 Curie Blvd., Philadelphia, 19104, Pennsylvania, USA

    Daniel Ricklin & John D Lambris

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Correspondence to John D Lambris.

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J.D.L., along with the University of Pennsylvania, has one issued and five pending patents on compstatin. These patents have been licensed for ophthalmic indications to Potentia Pharmaceuticals, Inc. J.D.L. is also a nonequity-holding member of the Scientific Advisory Board of Potentia Pharmaceuticals.

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Ricklin, D., Lambris, J. Complement-targeted therapeutics. Nat Biotechnol 25, 1265–1275 (2007). https://doi.org/10.1038/nbt1342

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