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Published on: October 28, 2022
Human single-chain variable fragment that specifically targets arthritic cartilage.
Chris Hughes1, Bjarne Faurholm, Francesco Dell'Accio
1Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
Arthritis and Rheumatism
|February 5, 2010
Summary
Researchers developed antibodies targeting reactive oxygen species-modified type II collagen (ROS-CII) found in damaged cartilage. These antibodies successfully targeted inflamed arthritic joints in mice, reducing inflammation and showing potential for arthritis therapeutics.
Area of Science:
- Biochemistry and Molecular Biology
- Immunology
- Rheumatology
Background:
- Reactive oxygen species (ROS) are present in inflamed arthritic joints.
- ROS can modify type II collagen (CII), creating unique epitopes.
- These modified epitopes are specific to damaged cartilage in rheumatoid arthritis (RA) and osteoarthritis (OA).
Purpose of the Study:
- To demonstrate that ROS-modified CII generates epitopes specific to damaged arthritic cartilage.
- To establish antibodies targeting ROS-modified CII as a proof of concept for targeted therapeutics.
- To assess the potential of these antibodies for specifically targeting inflamed arthritic joints.
Main Methods:
- A phage display human antibody library was used to generate single-chain variable fragments (scFv) against ROS-modified CII.
- Specificity was assessed in vitro using immunostaining of human arthritic and normal cartilage.
- In vivo targeting was evaluated in mice with antigen-induced arthritis, assessing joint localization and therapeutic effects of fused antibodies.
Main Results:
- Anti-ROS-modified CII scFv selectively bound to damaged cartilage from RA and OA patients, not normal cartilage.
- Systemic administration of anti-ROS-modified CII scFv led to selective accumulation in inflamed joints of arthritic mice.
- Fusion of anti-ROS-modified CII scFv to mTNFRII-Fc significantly reduced joint inflammation in mice.
Conclusions:
- Biologic therapeutics can be effectively targeted to arthritic joints using antibodies against ROS-modified CII.
- This approach offers a novel strategy for developing targeted treatments for arthritis.
- Targeting ROS-modified CII represents a promising new avenue for arthritis therapy.