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Killing arthritogenic fibroblast-like synoviocytes: an example using cytotoxic aptamers binding nucleolin
George D Kalliolias1, Efthimia K Basdra1, Athanasios G Papavassiliou2
1Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece.
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.
Insights
Difficult-to-treat rheumatoid arthritis (RA) involves specific synovial subtypes resistant to immunosuppression. Targeting arthritogenic fibroblast-like synoviocytes (FLS) with novel aptamers offers a promising new strategy for RA treatment.
Area of Science:
- Immunology
- Molecular Biology
- Rheumatology
Background:
- Certain rheumatoid arthritis (RA) subtypes, characterized by pauci-immune and fibroblast-rich synovium, resist standard immunosuppressive therapies.
- These difficult-to-treat (D2T) RA endotypes necessitate novel therapeutic strategies.
- Arthritogenic fibroblast-like synoviocytes (FLS) are key drivers in these RA subtypes.
Discussion:
- Single-cell profiling has identified distinct subpopulations of arthritogenic FLS.
- Molecular engineering advances have led to targeted therapies, including anti-FLS antibodies and T-cell engagers.
- These approaches aim for selective depletion of pathogenic FLS subpopulations.
Key Insights:
- Selective depletion of arthritogenic FLS is a promising strategy for D2T RA.
- Apoptosis-promoting aptamers represent a novel addition to the FLS-targeting therapeutic pipeline.
- This expands the armamentarium against difficult-to-treat rheumatoid arthritis.
Outlook:
- Further research into FLS-targeting therapies could revolutionize RA treatment.
- Development of highly selective agents may improve patient outcomes in resistant RA cases.
- Integration of aptamer technology offers new avenues for precision medicine in rheumatology.
