Development of Beta-Amyloid-Specific CAR-Tregs for the Treatment of Alzheimer’s Disease
Valerie Saetzler, Tobias Riët, Andrea Schienke, Pierre Henschel, Kiara Freitag, Alexander Haake, Frank L. Heppner, Laura Elisa Buitrago‐Molina, Fatih Noyan, Elmar Jaeckel, Matthias Hardtke‐Wolenski
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.