CAR T-Cell Therapy Offers New Hope for Systemic Sclerosis, Signaling a Potential Paradigm Shift in Autoimmune Treatment
For patients battling systemic sclerosis (SSc), a chronic and often debilitating autoimmune disease, a new beacon of hope has emerged. Recent data presented at ACR Convergence 2025 reveals that a single infusion of BMS-986353, a CD19-directed CAR T-cell therapy, not only improved lung function and skin thickness in severely affected individuals but also allowed an astonishing 96% to discontinue all SSc-directed therapies. This isn’t just incremental progress; it suggests a potential for long-term remission – a concept previously considered unattainable for many with this challenging condition.
Understanding the Breakfree-1 Trial and the Power of CAR T-Cells
The promising results stem from the Phase 1 Breakfree-1 trial, led by Dr. Dinesh Khanna of the University of Michigan. This trial investigated the efficacy and safety of BMS-986353 in 26 patients with severe, refractory SSc – meaning the disease hadn’t responded to conventional treatments. The therapy leverages the power of chimeric antigen receptor (CAR) T-cell therapy, a revolutionary approach that reprograms a patient’s own immune cells to target and eliminate disease-causing cells. Specifically, BMS-986353 targets CD19, a protein found on B cells, which play a critical role in the autoimmune processes driving SSc.
How BMS-986353 Differs from Existing CAR T-Cell Therapies
What sets BMS-986353 apart is its manufacturing process, utilizing the NEX-T platform. This innovative approach aims to shorten production time and optimize the characteristics of the CAR T-cells. Importantly, the CAR construct used in BMS-986353 is the same as that found in lisocabtagene maraleucel (Breyanzi), already approved for certain lymphomas, suggesting a well-understood safety profile and potential for streamlined regulatory pathways. This shared foundation could accelerate the availability of this treatment for SSc patients.
Significant Clinical Improvements and Durable Remission Potential
The trial data revealed robust CAR T-cell expansion and complete depletion of B cells in all patients. Beyond the impressive 96% therapy-free rate, researchers observed meaningful improvements in key disease markers. Median relative pulmonary function capacity (pFVC) increased by 10% in patients with SSc-ILD (interstitial lung disease) at 6 months, while median modified Rodnan Skin Score (mRSS) – a measure of skin thickening – decreased by 13.5 points in those with diffuse SSc. Furthermore, autoantibody levels, such as ANA and anti-RNA polymerase III, normalized over time in all patients who initially tested positive.
Managing Side Effects and Looking Ahead
While CAR T-cell therapy is known for potential side effects, the Breakfree-1 trial demonstrated a manageable safety profile. Most adverse events, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), were low-grade and resolved quickly with standard management. Two patients experienced transient grade-3 ICANS events, but these also resolved completely within five days. This suggests that the risks associated with BMS-986353 are acceptable, given the potential benefits for this severely ill population.
The Future of Autoimmune Treatment: Beyond SSc
The success of BMS-986353 in SSc has far-reaching implications. It validates the potential of CAR T-cell therapy as a disease-modifying treatment for autoimmune diseases, moving beyond symptom management towards achieving durable remission. Researchers are now exploring the application of CAR T-cell therapies targeting other B cell subsets or even different immune cells involved in other autoimmune conditions, such as lupus and rheumatoid arthritis. The National Institute of Arthritis and Musculoskeletal and Skin Diseases provides further information on systemic sclerosis and ongoing research.
The paradigm is shifting. We may be on the cusp of an era where a single, targeted therapy can fundamentally reset the immune system, offering lasting relief and improved quality of life for individuals with previously intractable autoimmune diseases. What are your predictions for the role of CAR T-cell therapy in treating autoimmune conditions? Share your thoughts in the comments below!
