COMPREHENSIVE analysis of 29 clinical trials evaluates chimeric antigen receptor cellular therapies for systemic sclerosis patients. As cell-based immunotherapies transition from oncology into rheumatology, understanding the current clinical trial landscape is vital for clinicians managing severe connective tissue diseases. A systematic review evaluating registered clinical trials highlights rapid expansion alongside significant heterogeneity in trial methodology, patient selection, and therapeutic constructs.
Researchers systematically searched international trial registries to analyze active studies investigating chimeric antigen receptor T-cell modalities in scleroderma. Among 29 actively recruiting trials identified, the overwhelming majority focus on CD19, with 27 studies targeting CD19 either as a monotherapy construct or through dual-targeting platforms alongside B-cell maturation antigen. Isolated targets against CD20 or B-cell maturation antigen are represented in individual trials. Autologous products dominate the current research footprint across 20 trials, whereas allogeneic off-the-shelf constructs account for nine protocols.
Despite expanding clinical interest, trial methodology remains predominantly early phase and non-comparative. Only two active protocols incorporate randomized trial designs, and a single study includes an active comparator arm utilizing rituximab. Patient enrollment is largely centered on early diffuse cutaneous systemic sclerosis, frequently embedded within broader autoimmune basket trials rather than dedicated disease-specific cohorts. Furthermore, interstitial lung disease eligibility criteria demonstrate marked inconsistency across registry entries, remaining completely unspecified in 22 trials.
Early clinical reporting demonstrates therapeutic feasibility and favorable safety profiles. Multicenter updates and case series involving diffuse cutaneous disease reveal deep B-cell depletion, manageable low-grade cytokine release, and encouraging preliminary improvements in skin thickness and pulmonary parameters. Most protocols mandate lymphodepletion preconditioning and rigorous immunosuppression washouts prior to cell infusion.
To translate these early clinical signals into scalable therapeutic options, researchers emphasize four critical priorities. Trial sponsors must establish harmonized eligibility criteria and standardized outcome measures across cellular programs. Future research requires larger multicenter trials with active comparators or delayed-start control arms. Finally, transparent reporting of patient subsets, including interstitial lung disease manifestations, remains essential to clarify treatment timing and preserve equitable clinical access.
Reference
Toro-Gutierrez C et al. Are We Putting the “Cart” Before the Horse in Systemic Sclerosis? A Review of the CAR-T Studies in Scleroderma. J Rheumatol. 2026;53(Suppl 1):152-153.
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