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Published on: May 4, 2017
Local complement inhibition by selective precision-targeted therapies
Haiyu Wang1, Daan J van den Brink1, Balthasar A Heesters2
1Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands.
Insights
Targeted complement inhibitors offer a promising new strategy for treating diseases caused by excessive complement activation. Local inhibition reduces risks and costs compared to systemic approaches.
Area of Science:
- Immunology
- Pharmacology
Background:
- Excessive complement activation is a key factor in numerous serious human diseases.
- Current complement inhibitors are typically administered systemically, leading to high costs and increased infection risks.
Purpose of the Study:
- To review novel strategies for local complement inhibition.
- To focus on tissue-specific targeting using antibody technologies for complement inhibition.
Main Methods:
- Review of preclinical and clinical development approaches for local complement inhibition.
- Focus on antibody-based tissue-specific targeting strategies.
Main Results:
- Local complement inhibition offers potential for lower dosing, reduced costs, and improved safety profiles.
- Tissue-specific targeting via antibody technologies is a key area of development.
Conclusions:
- Targeted complement inhibitors hold significant promise for selective inhibition at disease sites.
- Upcoming therapies aim to mitigate risks associated with systemic complement inhibition.
Abstract:
Excessive complement activation represents a major pathogenic mechanism for a range of serious human diseases. Complement-inhibitory therapeutics have been approved for a number of rare and ultra-rare conditions, with several others in clinical development. The vast majority of these complement-targeted drugs act via systemic inhibition that requires high dosing with associated high cost and, in addition, carries increased risks for developing life-threatening infectious diseases. Local complement inhibition, allowing lower dosing, lower costs, and a better safety profile, therefore, represents an attractive novel strategy. Several approaches to achieve local complement inhibition, including local application and site-specific targeting, are being assessed. This review will primarily focus on the tissue-specific targeting using antibody technologies for approaches both in preclinical and clinical development, and discuss its advantages and limitations. Overall, we see great promise for an upcoming generation of targeted complement inhibitors that enable selective inhibition of complement exclusively at the site of disease.
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