ArticleAnnals of the rheumatic diseases2013
Targeted delivery of cytokine therapy to rheumatoid tissue by a synovial targeting peptide.
Article in Annals of the rheumatic diseases, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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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
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Systematic Review: Targeted Molecular Imaging of Angiogenesis and Its Mediators in Rheumatoid Arthritis.International journal of molecular sciences · 2022Pooled it
- Peptide-based targeted drug delivery strategies for osteoarthritis treatment.npj biomedical innovations · 2026Review
- Precision prediction of intervertebral disc degeneration in ankylosing spondylitis using a nomogram model reveals the pivotal role of Th2-type immune dysregulation.Frontiers in immunology · 2025Article
- Targeted Therapy of Antibody-Induced Autoimmune Arthritis Using Peptide-Guided Nanoparticles.International journal of molecular sciences · 2024Article
- The therapeutic potential of immunoengineering for systemic autoimmunity.Nature reviews. Rheumatology · 2024Review
- Peptide targeting improves the delivery and therapeutic index of glucocorticoids to treat rheumatoid arthritis.Journal of controlled release : official journal of the Controlled Release Society · 2024Article
- Danggui Buxue Decoction exerts its therapeutic effect on rheumatoid arthritis through the inhibition of Wnt/β-catenin signaling pathway.Journal of orthopaedic surgery and research · 2023Article
- Biomaterial strategies for improved intra-articular drug delivery.Journal of biomedical materials research. Part A · 2021Review
- Novel Bispecific Antibody for Synovial-Specific Target Delivery of Anti-TNF Therapy in Rheumatoid Arthritis.Frontiers in immunology · 2021Article
- Overcoming negatively charged tissue barriers: Drug delivery using cationic peptides and proteins.Nano today · 2020Article
- Articular Cartilage- and Synoviocyte-Binding Poly(ethylene glycol) Nanocomposite Microgels as Intra-Articular Drug Delivery Vehicles for the Treatment of Osteoarthritis.ACS biomaterials science & engineering · 2020Article
- A novel CNS-homing peptide for targeting neuroinflammatory lesions in experimental autoimmune encephalomyelitis.Molecular and cellular probes · 2020Article
- Interleukin-1 receptor antagonist (IL-1Ra) is more effective in suppressing cytokine-induced catabolism in cartilage-synovium co-culture than in cartilage monoculture.Arthritis research & therapy · 2019Article
- Peptide-targeted liposomal delivery of dexamethasone for arthritis therapy.Nanomedicine (London, England) · 2019Article
- Targeting the extracellular matrix for delivery of bioactive molecules to sites of arthritis.British journal of pharmacology · 2019Review
- Peptide-directed liposomal delivery improves the therapeutic index of an immunomodulatory cytokine in controlling autoimmune arthritis.Journal of controlled release : official journal of the Controlled Release Society · 2018Article
- Immunocytokines: a novel class of products for the treatment of chronic inflammation and autoimmune conditions.Drug discovery today · 2016Review
- Robust Therapeutic Efficacy of Matrix Metalloproteinase-2-Cleavable Fas-1-RGD Peptide Complex in Chronic Inflammatory Arthritis.PloS one · 2016Article
- Rational design of antirheumatic prodrugs specific for sites of inflammation.Arthritis & rheumatology (Hoboken, N.J.) · 2015Article
- Trojan horses and guided missiles: targeted therapies in the war on arthritis.Nature reviews. Rheumatology · 2015Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
objectivesThe synovial endothelium targeting peptide (SyETP) CKSTHDRLC has been identified previously and was shown to preferentially localise to synovial xenografts in the human/severe combined immunodeficient (SCID) mouse chimera model of rheumatoid arthritis (RA). The objective of the current work was to generate SyETP-anti-inflammatory-cytokine fusion proteins that would deliver bioactive cytokines specifically to human synovial tissue.
methodsFusion proteins consisting of human interleukin (IL)-4 linked via a matrix metalloproteinase (MMP)-cleavable sequence to multiple copies of either SyETP or scrambled control peptide were expressed in insect cells, purified by Ni-chelate chromatography and bioactivity tested in vitro. The ability of SyETP to retain bioactive cytokine in synovial but not control skin xenografts in SCID mice was determined by in vivo imaging using nano-single-photon emission computed tomography-computed tomography (nano-SPECT-CT) and measuring signal transducer and activator of transcription 6 (STAT6) phosphorylation in synovial grafts following intravenous administration of the fusion protein.
resultsIn vitro assays confirmed that IL-4 and the MMP-cleavable sequence were functional. IL-4-SyETP augmented production of IL-1 receptor antagonist (IL-1ra) by fibroblast-like synoviocytes (FLS) stimulated with IL-1β in a dose-dependent manner. In vivo imaging showed that IL-4-SyETP was retained in synovial but not in skin tissue grafts and the period of retention was significantly enhanced through increasing the number of SyETP copies from one to three. Finally, retention correlated with increased bioactivity of the cytokine as quantified by STAT6 phosphorylation in synovial grafts.
conclusionsThe present work demonstrates that SyETP specifically delivers fused IL-4 to human rheumatoid synovium transplanted into SCID mice, thus providing a proof of concept for peptide-targeted tissue-specific immunotherapy in RA. This technology is potentially applicable to other biological treatments providing enhanced potency to inflammatory sites and reducing systemic toxicity.
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Registered trials
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