The ASGPR-CAR – a liver-specific chimeric antigen receptor
Keywords
Chimeric Antigen Receptor, Liver-Specific, ASGPR, regulatory T-cells, Immunotherapy
Invention Novelty
The novel technology reveals a liver-specific chimeric antigen receptor (CAR) targeting the Asialoglycoprotein-Receptor (ASGPR). Noteworthy, ASGPR is predominantly expressed on hepatocytes and is therefore an excellent antigen for liver-directed immunotherapy. The newly engineered single-chain variable fragment (scFv) with high specificity for ASGPR enables various immunotherapeutic approaches, in particular including the application in regulatory T-cells (Tregs).
Value Proposition
CAR-Tregs have the unique capability to modulate immune responses with high precision, making them promising candidates for enhancing tolerance in liver transplantation and for treating autoimmune liver diseases. In the context of transplantation, the precise targeting of ASGPR may significantly increase the likelihood of graft acceptance, while in autoimmune liver diseases, the approach could selectively suppress pathological immune responses without compromising the overall immune system. Therefore, considerable therapeutic and economic potential can be anticipated in the ASGPR-CAR.
“Homing” of murine Treg cells expressing an ASGPR-CAR into liver tissue.
Technology Description
The present invention comprises a novel CAR for use in patients with the need of liver-specific immunotherapy. Unlike previously developed CAR constructs targeting receptors such as the low-density lipoprotein (LDL) receptor, the newly developed ASGPR-CAR offers a superior approach by making use of ASGPR’s hepatocyte-specific expression profile. The herewith increased specificity minimizes off-target effects and enhances the therapeutic potential of ASGPR-CAR Tregs. In vivo studies using a mouse model confirmed that Treg cells expressing the CAR preferentially migrated into the liver and that their suppressor activity was activated essentially in liver only. Thus, a single transfer of ASGPR-specific Tregs could contribute to a long-lasting immunological tolerance.
Commercial Opportunity
In-licensing is possible.
Development Status
In vitro and in vivo studies have demonstrated the high selectivity and functional efficacy of ASGPR-modified CAR-Tregs.
Patent Situation
EP and US patent application based on WO 2024/208756 with priority of 2023 are pending.
Further Reading
Seltrecht N, Hardtke-Wolenski M, Iordanidis K, Jonigk D, Galla M, Schambach A, Buitrago-Molina LE, Wedemeyer H, Noyan F, Jaeckel E. 2024.Graft-Specific Regulatory T Cells for Long-Lasting, Local Tolerance Induction. Cells. 13(14):1216. doi: 10.3390/cells13141216.
Institute of Origin
