Engineering immune cell therapies for inflammatory bowel disease: from stem cells to CAR T cells

Despite the development of novel small molecules and antibody-based therapies targeting pro-inflammatory immune pathways, the clinical management of inflammatory bowel disease (IBD) remains challenging. In this Perspective, we highlight emerging treatment strategies with a focus on engineered cellular immunotherapies, including stem cell-based approaches, regulatory T cell and type 1 regulatory T cell therapies, as well as chimeric antigen receptor (CAR) T cell platforms (CAR T cells, CAR T_reg cells). Early-stage studies using haematopoietic and mesenchymal stem cells have yielded promising clinical results, although the safety and efficacy of such therapies require further careful validation. Moreover, efforts in immune cell engineering are now directed towards the expansion and adoptive transfer of allogeneic IL-10-producing type 1 regulatory T cells and autologous transforming growth factor-β-secreting regulatory T cells, which are currently being evaluated in early-stage clinical trials. Notably, a recent case report demonstrated that CD19-targeted CAR T cell therapy can induce long-term remission of intestinal inflammation in ulcerative colitis, highlighting a potential pathogenic role of mucosal B cells and plasmablasts in ulcerative colitis and underscoring the transformative therapeutic potential of CAR T cell strategies in IBD. Although these approaches offer exciting therapeutic prospects in IBD, rigorous prospective and controlled clinical trials are essential to fully assess their safety and efficacy.