Killing arthritogenic fibroblast-like synoviocytes: an example using cytotoxic aptamers binding nucleolin
- PMID: 40660355
- PMCID: PMC12261783
- DOI: 10.1186/s13075-025-03618-4
Killing arthritogenic fibroblast-like synoviocytes: an example using cytotoxic aptamers binding nucleolin
Abstract
"Pauci-immune" and "fibroblast-rich" synovial pathotypes are predictors of resistance to multi-drug immunosuppression. For these "difficult-to-treat" (D2T) endotypes of rheumatoid arthritis (RA), depletion of arthritogenic fibroblast-like synoviocytes (FLS) has emerged as promising treatment strategy. Profiling at a single-cell level has enabled the molecular characterization of distinct subpopulations of arthritogenic FLS. Advances in molecular engineering have empowered the development of multiple modalities (anti-FLS antibodies, T-cell engagers, cytotoxic cells with chimeric receptors recognizing FLS-specific antigens) to achieve depletion of arthritogenic subpopulations of FLS with unprecedented selectivity. A recently published study highlighted in this article, adds apoptosis-promoting aptamers in the armamentarium of the FLS-killing pipeline.
Keywords: Aptamers; Fibroblast-like synoviocytes; Nucleolin; Rheumatoid arthritis; Treatment.
© 2025. The Author(s).
Conflict of interest statement
Declarations. Consent for publication: All authors agreed to the publication of this manuscript. Competing interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
References
-
- Källmark H, Einarsson JT, Nilsson JÅ, et al. Sustained remission in patients with rheumatoid arthritis receiving triple therapy compared to biologic therapy: A Swedish nationwide register study. Arthritis Rheumatol. 2021;73(7):1135–44. 10.1002/art.41720. - PubMed
-
- Humby F, Durez P, Buch MH, et al. Rituximab versus Tocilizumab in anti-TNF inadequate responder patients with rheumatoid arthritis (R4RA): 16-week outcomes of a stratified, biopsy-driven, multicentre, open-label, phase 4 randomised controlled trial. Lancet. 2021;397:305–17. 10.1016/S0140-6736(20)32341-2. - PMC - PubMed
-
- Rivellese F, Nerviani A, Giorli G, et al. Stratification of biological therapies by pathobiology in biologic-naive patients with rheumatoid arthritis (STRAP and STRAP-EU): two parallel, open-label, biopsy-driven, randomised trials. Lancet Rheumatol. 2023;5:e648–659. 10.1016/S2665-9913(23)00241-2. - PubMed
-
- Qiu F, Xie D, Chen H, et al. Generation of cytotoxic aptamers specifically targeting fibroblast-like synoviocytes by CSCT-SELEX for treatment of rheumatoid arthritis. Ann Rheum Dis. 2025;84(5):726–45. 10.1136/ard-2024-225565. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
