A2
Novel CARs for the Treatment of Multiple Sclerosis and Alzheimer´s Disease
Prof. Matthias Hardtke-Wolenski, Hannover Medical School; Dr Valerie Sätzler, Hannover Medical School; Prof. Elmar Jäckel, Hannover Medical School; Dr Tobias Riet, Hannover Medical School; Prof. Michael Hust, Technische Universität Braunschweig; Saskia Helmsing, Technische Universität Braunschweig
Ascenion GmbH
Challenge
The invention introduces novel Chimeric Antigen Receptors (CARs) that are expressed in regulatory T-cells (Tregs) and enable targeted immunosuppression within the central nervous system. These CARs are uniquely specific to myelin basic protein (MBP) or myelin oligodendrocyte glycoprotein (MOG) and provide an immunotherapeutic strategy for treating autoimmune neuroinflammatory diseases with a focus on MS and AD. Engineered Tregs with antigen-specific CARs targeting MBP or MOG ensure localized immunosuppression specifically within the brain and spinal cord. A major value lies in the ability of Tregs to migrate naturally to diseased neuronal tissues, including migrating across the blood-brain barrier, allowing for systemic administration while achieving localized effects. Furthermore, a built-in safety marker provides the capacity for selective cell deletion, addressing a critical safety concern in cell-based therapies.
Technology
The described technology consists of modified Tregs that express CARs targeting either MBP or MOG. The characteristic single chain variable fragments (scFvs) were derived via phage display for high affinity to MBP or MOG and fused to intracellular signaling domains. Further, the CAR is co-expressed with FOXP3 to ensure the regulatory phenotype of Tregs, and optionally coupled to a safety marker. Tregs are derived from autologous T-cells and genetically modified to express the CAR. In vitro and in vivo studies showed target-specific activation of novel CAR-Tregs and high specificity to CNS tissue in a disease-related mouse model. In summary, the technology enables an antigen-specific therapeutic approach with a clear potential to restore immune tolerance in neuroinflammatory autoimmune disorders without broad immunosuppression.
Commercial Opportunity
In-licensing or collaboration for further development is possible.
Development Status
In vitro and in vivo studies have successfully demonstrated proof of concept of the novel technology.
Patent Situation
EP and US patent application pending (based on WO 2025/040799) with priority of 2023.
Further Reading
Saetzler V, Riet T, Schienke A, Henschel P, Freitag K, Haake A, Heppner FL, Buitrago-Molina LE, Noyan F, Jaeckel E, Hardtke-Wolenski M. 2023. Development of Beta-Amyloid-Specific CAR-Tregs for the Treatment of Alzheimer's Disease. Cells. 12(16):2115. doi: 10.3390/cells12162115.
