Promising Results Seen With CAR T-Cell Therapy in Rare Lung Disease

October 26, 2025 | 3 min read

A one-time infusion of BMS-986353, a CD19 CAR T-cell therapy, improved lung function and skin thickness in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD), according to data presented at the American College of Rheumatology Convergence 2025.

Systemic sclerosis is a chronic autoimmune disease that causes hardening and tightening of the skin and connective tissues. SSc-ILD is a serious complication of the disease, leading to progressive lung scarring and respiratory failure. Current treatments offer limited efficacy, highlighting the need for novel therapies.

The phase 1/2 trial enrolled 15 patients with SSc-ILD who received a single infusion of BMS-986353.Researchers assessed changes in forced vital capacity (FVC), a measure of lung function, and modified Rodnan Skin Score (mRSS), which assesses skin thickness.

Approximately 80% of patients experienced a clinically meaningful advancement in FVC at 12 months,and a significant reduction in mRSS was observed. The therapy was generally well-tolerated, with most adverse events being manageable.

“These are very encouraging results,” said lead investigator [Insert Investigator name and Affiliation Here]. “CAR T-cell therapy has the potential to be a game-changer for patients with SSc-ILD, offering a new hope for improved lung function and quality of life.”

Researchers are continuing to follow patients in the trial to assess the long-term effects of BMS-986353. Further studies are planned to confirm these findings and explore the potential of CAR T-cell therapy in other autoimmune diseases.

Key takeaways:

* A one-time infusion of BMS-986353, a CD19 CAR T-cell therapy, improved lung function and skin thickness.
* Approximately 80% of patients experienced a clinically meaningful improvement in FVC at 12 months.
* The therapy was generally well-tolerated.

Promising Results with CAR T-Cell Therapy in Severe Refractory Systemic Sclerosis

Recent findings from the Breakfree-1 trial suggest that directed CAR T-cell therapy may offer a potential treatment option for patients with severe, refractory systemic sclerosis (SSc). Researchers, led by Khanna and colleagues, evaluated BMS-986353, a CAR T-cell therapy manufactured using the NEX-T process designed to expedite production and enhance cell characteristics. This process utilizes the same CAR construct as lisocabtagene maraleucel (Breyanzi), currently approved for specific non-Hodgkin lymphomas.

The analysis, with a data cutoff of August 14, included 26 patients with severe refractory disease – either recently progressing diffuse SSc or limited SSc with interstitial lung disease (ILD) – who had shown insufficient response to at least one immunosuppressant. Participants had high median modified Rodnan Skin Score (mRSS) scores, and 10 of the 19 patients assessed for efficacy had ILD. Prior to receiving a single infusion of BMS-986353 at either 10×106 (dosing level 1) or 25×106 (dosing level 2) CAR+ T cells, all patients discontinued existing SSc-directed therapies following lymphodepletion. The primary endpoint of the trial was safety.

Results indicated robust CD19 NEX-T-cell expansion and corresponding B-cell depletion in all patients. B cells were undetectable in the periphery by day 15 post-infusion. For patients with over one month of follow-up, the median time to B-cell repopulation was 113 days. Repopulating B cells were predominantly naive at day 141, with a reduction in memory and double-negative B cells. Furthermore, autoantibody levels, including ANA and anti-RNA polymerase III, decreased or normalized over time in all patients with abnormal baseline values.

The safety profile observed was consistent with that of CD19 CAR T-cell therapy. Most treatment-related adverse events occurred shortly after infusion and resolved quickly with standard management. Fourteen patients experienced cytokine release syndrome (CRS), all of which were low grade and resolved within a median of 2 days. Two transient, grade-3 immune effector cell-associated neurotoxicity syndrome (ICANS) events were also reported, resolving fully within 5 days.

Currently, 25 of the 26 patients have remained off SSc-directed treatments. One patient, with low pulmonary reserve at baseline but no clinical worsening, was treated with nintedanib.Importantly,no patients exhibited evidence of new disease activity.