Cellular therapies and immune reprogramming in inflammatory bowel disease: lessons learned and the promise of CAR T-cell therapy.

Authors

Tommaso L Parigi, Bianca N Islam, Theresa T Pizarro, Fabio Cominelli

Published in

Inflammatory bowel diseases. Nov 10, 2026. Epub Nov 10, 2026.

Abstract

Despite major therapeutic advances, inflammatory bowel disease (IBD) remains incurable, and many patients experience primary non-response, secondary loss of response, progressive bowel damage, or lifelong dependence on immunomodulatory therapy. Cellular immunotherapies offer the possibility of moving beyond chronic immune suppression toward durable immune reprogramming. Earlier approaches in IBD, including hematopoietic stem cell transplantation, mesenchymal stem cells, and regulatory T-cell-based therapies, have provided important proof-of-concept but have been limited by toxicity, inconsistent efficacy, local rather than systemic effects, or unresolved manufacturing and durability challenges. Chimeric antigen receptor (CAR) T-cell therapy represents the next-generation strategy that combines potent immune remodeling with antigen-specific targeting. Initially developed for hematological malignancies, CAR T cells have recently shown striking efficacy in refractory autoimmune diseases, particularly through CD19-mediated depletion of B-lineage cells and induction of drug-free remission. In ulcerative colitis, renewed interest in B cells has been driven by evidence of plasmablast expansion, IgG-skewed humoral responses, anti-integrin αvβ6 autoantibodies, and the limitations of conventional anti-CD20 depletion. The first reported case of multidrug-resistant ulcerative colitis treated with CD19 CAR T cells demonstrated rapid clinical, biochemical, endoscopic, and histological remission, providing proof-of-concept for deep B-cell targeting in IBD. However, major uncertainties remain, including long-term durability, relapse after B-cell reconstitution, safety, cost, feasibility, and the risk of CAR T-associated gastrointestinal toxicity. Prospective trials with mechanistic mucosal monitoring are now needed to define the therapeutic potential and appropriate positioning of CAR-based strategies in IBD.

PMID:
43007306
Bibliographic data and abstract were imported from PubMed on 10 Nov 2026.

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