CAR-T cells and CAR-Treg cells for treatment of inflammatory bowel diseases

Abstract

Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are therapeutically challenging chronic inflammatory diseases of the intestine. Despite major advances in biologic and small-molecule therapies, many patients with IBD experience primary nonresponse, secondary loss of response, or severe complications, underscoring the need for innovative therapeutic strategies that lead to sustained immune recalibration. Chimeric antigen receptor (CAR)-based cellular therapies represent an emerging new concept for transformative medicine. These CAR-T cells are engineered to recognise defined surface antigens, such as CD19, and are therefore ideally suited to eliminate selected pathogenic immune cell populations, such as B lymphocytes. In IBD, this concept has gained momentum through evidence implicating mucosal B cells, plasmablasts, and disease-associated humoral responses as potential disease drivers in UC. A recent case report suggested that CD19-directed CAR-T cell therapy may induce profound remission in multirefractory UC. In parallel, CAR regulatory T cells (CAR Tregs) may offer a complementary approach for IBD therapy by redirecting suppressive immune function in the inflamed intestine. Particularly, interleukin-23 receptor-targeted CAR Tregs provide a mechanistically attractive strategy to modulate T helper–type 17-driven mucosal inflammation in CD. Safety considerations and translational challenges are potential concerns with regard to CAR-T and CAR-Treg therapies in IBD. However, these technologies may enable precision immune engineering for selected refractory disease endotypes in IBD.