Emerging CAR-Treg and regulatory T cell therapies for inflammatory bowel diseases: a systematic review of a new era of treatment
TL;DR
Cellular immunotherapies represent a promising but still investigational therapeutic paradigm in IBD and robust clinical trials with standardized endpoints and long-term safety monitoring are needed before their clinical adoption.
Abstract
Background Inflammatory bowel disease (IBD) is a chronic immune-mediated disorder characterized by dysregulated mucosal immunity. Despite major advances in therapies, a high proportion of patients do not achieve or sustain remission. Cellular immunotherapies have emerged as a mechanistically distinct therapeutic strategy with potential relevance for refractory disease. In the present paper, the authors aim to evaluate the rationale and current evidence supporting chimeric antigen receptor (CAR)-engineered immune cells and regulatory T (Treg)-cell–based therapies in IBD. Preclinical studies and early translational data support biological plausibility and feasibility of these therapies. However, available human evidence remains limited, with sparse clinical experience and short follow-up. Methods A systematic review was conducted according to PRISMA guidelines. Search was performed in PubMed and EMBASE databases from inception to February 2026 including terms like “IBD”, “CAR-T”, “CAR-Treg” and “Treg therapy” among others. Eligible studies included preclinical, translational and clinical reports evaluating CAR-engineered immune cells in IBD models. Results A total of 11 studies met the inclusion criteria after the screening and were included in the review. CAR-Treg technologies build upon advances achieved with conventional CAR-T cells in oncology and enable antigen-specific immune regulation rather than cytotoxicity. Preclinical studies and early translational data support biological plausibility and feasibility. However, available human evidence remains limited, with sparse clinical experience and short follow-up. Major unresolved issues include cellular persistence, phenotypic stability (particularly for Tregs), optimal antigen selection, manufacturing scalability, and long-term safety. Conclusions Cellular immunotherapies represent a promising but still investigational therapeutic paradigm in IBD. Robust clinical trials with standardized endpoints and long-term safety monitoring are needed before their clinical adoption.