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Updated: Sep 12, 2025

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Depletion of Specific Cell Populations by Complement Depletion
Published on: February 5, 2010
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Eliciting or silencing complement activation: strategies for optimizing monoclonal antibodies functions
Axelle Amen1, Nicole Thielens2, Chantal Dumestre-Pérard1
1Univ. Grenoble Alpes, CNRS, CEA, UMR5075, IBS, Laboratoire d'Immunologie CHU Grenoble Alpes, 38000 Grenoble, France.
Current Opinion in Immunology
|August 8, 2025
Summary
Modulating complement activity is key for monoclonal antibody (mAb) therapies. Strategies to enhance or suppress complement are crucial for optimizing therapeutic effects and reducing side effects in various disease treatments.
Area of Science:
- Immunology
- Biotechnology
- Pharmacology
Background:
- Complement activity tuning is vital for monoclonal antibody (mAb) efficacy and safety.
- Enhancement strategies target pathogens and tumors; silencing strategies address autoimmune diseases and transplantation.
- Symmetrical approaches exist to modulate complement activation for therapeutic benefit.
Purpose of the Study:
- To review methods for enhancing or suppressing complement activity in mAb design.
- To highlight symmetrical strategies for precise complement modulation.
- To discuss the future of AI-driven mAb therapeutics with tailored complement control.
Main Methods:
- Isotype/subtype selection
- Fc region engineering (mutations)
- Glycosylation engineering
- Bispecific antibody design
- Fc-deficient formats
Main Results:
- Various protein engineering techniques allow for precise control over complement activation.
- Bispecific antibodies offer versatile ways to recruit or block complement regulators.
- Fc-deficient formats effectively eliminate complement-activating functions.
Conclusions:
- Tailored modulation of complement activity is central to next-generation mAb therapeutics.
- Advancements in complement biology and AI-driven design will enable sophisticated mAb engineering.
- Optimizing complement engagement is essential for maximizing therapeutic potential and minimizing adverse effects.
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