ArticleScientific reports2021
Selective activation of pro-anti-IL-1β antibody enhances specificity for autoinflammatory disorder therapy.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
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- Conditionally Activatable Antibody Platforms: Mechanisms, Modalities, and Clinical Translation Potential.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Use of Anti-interleukin-1 Agents in Kidney Transplant Recipients with Familial Mediterranean Fever and Amyloidosis: What have been learned so far?Current transplantation reports · 2025Article
- Encoded cell-material interactions to reroute cytokine signaling for regenerative medicine.bioRxiv : the preprint server for biology · 2025Article
- Advancing osteoarthritis management: integrating new insights and addressing persistent roadblocks.Inflammopharmacology · 2025Review
- Metabolic Reprogramming of Macrophages by Biomimetic Melatonin-Loaded Liposomes Effectively Attenuates Acute Gouty Arthritis in a Mouse Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Pro-Inflammatory and Anti-Inflammatory Interleukins in Infectious Diseases: A Comprehensive Review.Tropical medicine and infectious disease · 2024Review
- Network Pharmacology and Experimental Validation Explore the Pharmacological Mechanisms of Herb Pair for Treating Rheumatoid Arthritis.Combinatorial chemistry & high throughput screening · 2024Article
- CAR-T cells targeting HLA-G as potent therapeutic strategy for EGFR-mutated and overexpressed oral cancer.iScience · 2023Article
- A lesion-selective albumin-CTLA4Ig as a safe and effective treatment for collagen-induced arthritis.Inflammation and regeneration · 2023Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Canakinumab is a fully human monoclonal antibody that specifically neutralizes human interleukin (IL)-1β and has been approved by the US Food and Drug Administration for treating different types of autoinflammatory disorders such as cryopyrin-associated periodic syndrome, tumor necrosis factor receptor-associated periodic syndrome and systemic juvenile idiopathic arthritis. However, long-term systemic neutralization of IL-1β by Canakinumab may cause severe adverse events such as serious upper respiratory tract infections and inflammation, thereby decreasing the quality of life of patients. Here, we used an IgG1 hinge as an Ab lock to cover the IL-1β-binding site of Canakinumab by linking with matrix metalloprotease 9 (MMP-9) substrate to generate pro-Canakinumab that can be specifically activated in the inflamed regions in autoinflammatory diseases to enhance the selectivity and safety of treatment. The Ab lock significantly inhibited the IL-1β-binding by 68-fold compared with Canakinumab, and MMP-9 completely restored the IL-1β neutralizing ability of pro-Canakinumab within 60 min and blocked IL-1β-downstream signaling and IL-1β-regulated genes (i.e., IL-6). It is expected that MMP-9 cleavable and efficient Ab lock will be able to significantly enhance the selective reaction of Canakinumab at the disease site and reduce the on-target toxicities of Canakinumab during systemic circulation, thereby showing potential for development to improve the safety and quality of life of patients with autoinflammatory disorders in the future.
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