A Removable Lock for Monoclonal Antibody Arthritis Drugs May Improve the Effectiveness & Safety


Senior Member
'Locking' an arthritis drug may be key to improving it

Modification reduces systemic immune suppression and drug neutralization

June 13, 2019​
Attaching a removable lock to an arthritis drug can make it safer and more effective, according to a new study. The findings suggest a new way to improve the efficacy of a drug taken by millions of patients throughout the world.​
The monoclonal antibodies infliximab and adalimumab have become blockbuster drugs for the autoimmune disease rheumatoid arthritis, because of their ability to block the activity of tumor necrosis factor alpha (TNF-alpha), a key signaling molecule in the autoimmune cascade. But their use comes with two major drawbacks -- TNF-alpha blockade in non-arthritic tissues can lead to dangerous immune suppression, and many patients receiving the therapy quickly develop antibodies to the monoclonals themselves, thereby suppressing the activity of the drugs.

The authors set out to mitigate both problems by adding a removable protein "lock" to the infliximab antibody. They attached their lock by chemically linking it to the "business end" of the antibody using a protein tag that can be removed by an enzyme called matrix metalloproteinase (MMP). MMP is abundant at the site of rheumatoid arthritis, where it contributes to the tissue breakdown that is a major consequence of the disease. . . .

"The addition of this reversible lock to infliximab has the potential to improve the risk/benefit ratio for patients with rheumatoid arthritis," . . . and may serve as a model for improvement of other monoclonal antibody therapies as well. . . .
Specific activation of pro-Infliximab enhances selectivity and safety of rheumatoid arthritis therapy. PLOS Biology, 2019; 17 (6): e3000286 DOI: 10.1371/journal.pbio.3000286