TSHR-based chimeric antigen receptor T cell specifically deplete auto-reactive B lymphocytes for treatment of autoimmune thyroid disease
Highlights
Graves' disease (GD) is a prominent antibody-mediated autoimmune disorder characterized by stimulating antibodies (TRAb) that target the thyroid-stimulating hormone receptor (TSHR). Targeting and eliminating TRAb-producing B lymphocytes hold substantial therapeutic potential for GD. In this study, we engineered a novel chimeric antigen receptor T cell (CAR-T) therapy termed TSHR-CAR-T. This CAR-T construct incorporates the extracellular domain of the TSH receptor fused with the CD8 transmembrane and intracellular signal domain (4-1BB). TSHR-CAR-T cells demonstrated the ability to recognize and effectively eliminate TRAb-producing B lymphocytes both in vitro and in vivo. Leveraging this autoantigen-based chimeric receptor, our findings suggest that TSHR-CAR-T cells offer a promising and innovative immunotherapeutic approach for the treatment of antibody-mediated autoimmune diseases, including GD.
https://www.sciencedirect.com/science/article/pii/S1567576923011980
Highlights
- Graves disease (GD), a typical organ-specific, antibody-mediated autoimmune disease, is caused by stimulating antibody which recognizes TSHR (TRAb)
- Therefore, specifically, eliminating TRAb producing B lymphocytesmay be an effective therapeutic strategy for GD.
- In this study, we developed a chimeric receptor TSHR-CAR, which fused TSHR extracellular domain to the CD8 transmembrane and intracellular signal domain (4-1BB)
- TSHR-CAR-T cells can specifically recognize and exert a cytotoxic effect on TRAb producing B lymphocytes of mice in vivo and in vitro.
- The chimeric receptor CAR-T based on autoantigen may provide promising immunotherapy for antibody-mediated autoimmune diseases.
Graves' disease (GD) is a prominent antibody-mediated autoimmune disorder characterized by stimulating antibodies (TRAb) that target the thyroid-stimulating hormone receptor (TSHR). Targeting and eliminating TRAb-producing B lymphocytes hold substantial therapeutic potential for GD. In this study, we engineered a novel chimeric antigen receptor T cell (CAR-T) therapy termed TSHR-CAR-T. This CAR-T construct incorporates the extracellular domain of the TSH receptor fused with the CD8 transmembrane and intracellular signal domain (4-1BB). TSHR-CAR-T cells demonstrated the ability to recognize and effectively eliminate TRAb-producing B lymphocytes both in vitro and in vivo. Leveraging this autoantigen-based chimeric receptor, our findings suggest that TSHR-CAR-T cells offer a promising and innovative immunotherapeutic approach for the treatment of antibody-mediated autoimmune diseases, including GD.
https://www.sciencedirect.com/science/article/pii/S1567576923011980