ArticleArthritis & rheumatology (Hoboken, N.J.)2015
Rational design of antirheumatic prodrugs specific for sites of inflammation.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Article
- Design of a prodrug bispecific antibody masked by a functional molecule for lymphocyte activation for cancer therapy.Journal of biological engineering · 2025Article
- Fibronectin-targeted FUD and PEGylated FUD peptides for fibrotic diseases.Journal of controlled release : official journal of the Controlled Release Society · 2023Article
- Exploiting protease activation for therapy.Drug discovery today · 2022Review
- The Masking Game: Design of Activatable Antibodies and Mimetics for Selective Therapeutics and Cell Control.ACS central science · 2021Review
- Novel Bispecific Antibody for Synovial-Specific Target Delivery of Anti-TNF Therapy in Rheumatoid Arthritis.Frontiers in immunology · 2021Article
- Ab locks for improving the selectivity and safety of antibody drugs.Journal of biomedical science · 2020Review
- The Dual Role of the Liver in Nanomedicine as an Actor in the Elimination of Nanostructures or a Therapeutic Target.Journal of oncology · 2020Review
- Targeting the extracellular matrix for delivery of bioactive molecules to sites of arthritis.British journal of pharmacology · 2019Review
- Review
- Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveBiologic drugs, such as the anti-tumor necrosis factor (anti-TNF) antibody adalimumab, have represented a breakthrough in the treatment of rheumatoid arthritis. Yet, concerns remain over their lack of efficacy in a sizable proportion of patients and their potential for systemic side effects such as infection. Improved biologic prodrugs specifically targeted to the site of inflammation have the potential to alleviate current concerns surrounding biologic anticytokine therapies. The purpose of this study was to design, construct, and evaluate in vitro and ex vivo the targeting and antiinflammatory capacity of activatable bispecific antibodies.
methodsActivatable dual variable domain (aDVD) antibodies were designed and constructed to target intercellular adhesion molecule 1 (ICAM-1), which is up-regulated at sites of inflammation, and anti-TNF antibodies (adalimumab and infliximab). These bispecific molecules included an external arm that targets ICAM-1 and an internal arm that comprises the therapeutic domain of an anti-TNF antibody. Both arms were linked to matrix metalloproteinase (MMP)-cleavable linkers. The constructs were tested for their ability to bind and neutralize both in vitro and ex vivo targets.
resultsIntact aDVD constructs demonstrated significantly reduced binding and anti-TNF activity in the prodrug formulation as compared to the parent antibodies. Human synovial fluid and physiologic concentrations of MMP enzyme were capable of cleaving the external domain of the antibody, revealing a fully active molecule. Activated antibodies retained the same binding and anti-TNF inhibitory capacities as the parent molecules.
conclusionThe design of a biologic prodrug with enhanced specificity for sites of inflammation (synovium) and reduced specificity for off-target TNF is described. This construct has the potential to form a platform technology that is capable of enhancing the therapeutic index of drugs for the treatment of RA and other inflammatory diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.