Development of Beta-Amyloid-Specific CAR-Tregs for the Treatment of Alzheimer’s Disease
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 inflamm...
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MDPI AG
2023-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/16/2115 |
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| author | Valerie Saetzler Tobias Riet Andrea Schienke Pierre Henschel Kiara Freitag Alexander Haake Frank L. Heppner Laura Elisa Buitrago-Molina Fatih Noyan Elmar Jaeckel Matthias Hardtke-Wolenski |
| author_facet | Valerie Saetzler Tobias Riet Andrea Schienke Pierre Henschel Kiara Freitag Alexander Haake Frank L. Heppner Laura Elisa Buitrago-Molina Fatih Noyan Elmar Jaeckel Matthias Hardtke-Wolenski |
| author_sort | Valerie Saetzler |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T00:02:54Z |
| format | Article |
| id | doaj.art-f72eecfb2b00440c95d4793a333c7460 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T00:02:54Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-f72eecfb2b00440c95d4793a333c74602023-11-19T00:37:47ZengMDPI AGCells2073-44092023-08-011216211510.3390/cells12162115Development of Beta-Amyloid-Specific CAR-Tregs for the Treatment of Alzheimer’s DiseaseValerie Saetzler0Tobias Riet1Andrea Schienke2Pierre Henschel3Kiara Freitag4Alexander Haake5Frank L. Heppner6Laura Elisa Buitrago-Molina7Fatih Noyan8Elmar Jaeckel9Matthias Hardtke-Wolenski10Department of Gastroenterology, Hepatology, Infectious Diseases & Endocrinology, Hannover Medical School, 30625 Hannover, GermanyDepartment of Gastroenterology, Hepatology, Infectious Diseases & Endocrinology, Hannover Medical School, 30625 Hannover, GermanyDepartment of Gastroenterology, Hepatology, Infectious Diseases & Endocrinology, Hannover Medical School, 30625 Hannover, GermanyDepartment of Gastroenterology, Hepatology, Infectious Diseases & Endocrinology, Hannover Medical School, 30625 Hannover, GermanyDepartment of Neuropathology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, GermanyDepartment of Neuropathology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, GermanyDepartment of Neuropathology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, GermanyDepartment of Gastroenterology, Hepatology, Infectious Diseases & Endocrinology, Hannover Medical School, 30625 Hannover, GermanyDepartment of Gastroenterology, Hepatology, Infectious Diseases & Endocrinology, Hannover Medical School, 30625 Hannover, GermanyDepartment of Gastroenterology, Hepatology, Infectious Diseases & Endocrinology, Hannover Medical School, 30625 Hannover, GermanyDepartment of Gastroenterology, Hepatology, Infectious Diseases & Endocrinology, Hannover Medical School, 30625 Hannover, GermanyBackground: 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.https://www.mdpi.com/2073-4409/12/16/2115chimeric antigen receptorAlzheimer’s diseasebeta-amyloidregulatory T cellssingle-chain fragment |
| spellingShingle | Valerie Saetzler Tobias Riet Andrea Schienke Pierre Henschel Kiara Freitag Alexander Haake Frank L. Heppner Laura Elisa Buitrago-Molina Fatih Noyan Elmar Jaeckel Matthias Hardtke-Wolenski Development of Beta-Amyloid-Specific CAR-Tregs for the Treatment of Alzheimer’s Disease Cells chimeric antigen receptor Alzheimer’s disease beta-amyloid regulatory T cells single-chain fragment |
| title | Development of Beta-Amyloid-Specific CAR-Tregs for the Treatment of Alzheimer’s Disease |
| title_full | Development of Beta-Amyloid-Specific CAR-Tregs for the Treatment of Alzheimer’s Disease |
| title_fullStr | Development of Beta-Amyloid-Specific CAR-Tregs for the Treatment of Alzheimer’s Disease |
| title_full_unstemmed | Development of Beta-Amyloid-Specific CAR-Tregs for the Treatment of Alzheimer’s Disease |
| title_short | Development of Beta-Amyloid-Specific CAR-Tregs for the Treatment of Alzheimer’s Disease |
| title_sort | development of beta amyloid specific car tregs for the treatment of alzheimer s disease |
| topic | chimeric antigen receptor Alzheimer’s disease beta-amyloid regulatory T cells single-chain fragment |
| url | https://www.mdpi.com/2073-4409/12/16/2115 |
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