Can chimeric antigen receptors - based therapy bring a gleam of hope for thyroid-associated ophthalmopathy and other autoimmune diseases?

Abstract

Thyroid-associated ophthalmopathy (TAO), also known as Graves' ophthalmopathy (GO) is an autoimmune disease (AD) with abnormal thyroid function typically. Currently, intravenous glucocorticoid therapy remains the first-line treatment for moderate-to-severe active TAO. Second-line treatments, including immunosuppressants and biological agents, are being explored in depth. However, like other ADs, the adverse effects of these therapies, little impact on long-term sequelae, and the irreversible progression of the disease remain significant limitations. As a result, the development of new therapeutic strategies for TAO is essential. Chimeric antigen receptors (CAR)-based adoptive cell therapy has emerged as an innovative approach for ADs treatment, capitalizing on its principles of genetically modifying immune cells to specifically target pathogenic cells. This approach aims to reduce autoimmune response or eliminate effective cells, CAR-based therapies of both T-cell-mediated and B-cell-mediated ADs have shown promising results in wide clinical trial. CAR-based therapy obviously become a rising star on refractory and relapsed ADs. TAO is no exception in terms of the potential for improvement through CAR-based therapy. However, the success of CAR-based therapy in TAO depends critically on identifying appropriate targets. Selected targets need to be coverage to ensure the therapeutic efficiency while specificity to preserve safety. Furthermore, the target cells must be relevant to the pathogenesis of TAO. Except target selection, adopting advanced and effective strategies for CAR design is also crucial. For example, dual-target approaches involving thyroid-stimulating hormone receptor (TSHR) or insulin-like growth factor-1 receptor (lGF-1R), off-the-shelf CAR-based cells, or leveraging artificial intelligence (Al) to predict optimal targets could enhance the specificity and effectiveness of CAR-based, therapies in TAO treatment.