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- Title
Development of Beta-Amyloid-Specific CAR-Tregs for the Treatment of Alzheimer's Disease.
- Authors
Saetzler, Valerie; Riet, Tobias; Schienke, Andrea; Henschel, Pierre; Freitag, Kiara; Haake, Alexander; Heppner, Frank L.; Buitrago-Molina, Laura Elisa; Noyan, Fatih; Jaeckel, Elmar; Hardtke-Wolenski, Matthias
- Abstract
Background: Alzheimer's disease (AD) is a neurodegenerative disease that remains uncured. Its pathogenesis is characterized by the formation of β-amyloid (Aβ) plaques. The use of antigen-specific regulatory T cells (Tregs) through adoptive transfer has shown promise for the treatment of many inflammatory diseases, although the effectiveness of polyspecific Tregs is limited. Obtaining a sufficient number of antigen-specific Tregs from patients remains challenging. Aims and Methods: To address this problem, we used an antibody-like single-chain variable fragment from a phage library and subsequently generated a chimeric antigen receptor (CAR) targeting β-amyloid. Results: The β-amyloid-specific CARs obtained were stimulated by both recombinant and membrane-bound Aβ isolated from the murine brain. The generated CAR-Tregs showed a normal Treg phenotype, were antigen-specific activatable, and had suppressive capacity. Conclusion: This study highlights the potential of CAR technology to generate antigen-specific Tregs and presents novel approaches for developing functional CARs.
- Subjects
ALZHEIMER'S disease; REGULATORY T cells; IMMUNOGLOBULINS; CHIMERIC antigen receptors; MONOCLONAL antibodies; NEURODEGENERATION
- Publication
Cells (2073-4409), 2023, Vol 12, Issue 16, p2115
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells12162115