Dual-Target CD19/BCMA CAR T-Cell Therapy Demonstrates Profound Remission in Refractory Systemic Sclerosis
核心洞察
All 11 patients with refractory systemic sclerosis (搜索) achieved rapid B-cell aplasia following dual-target CD19/BCMA CAR T-cell therapy (搜索), with significant improvements in skin thickness scores.
Modified Rodnan Skin Score improved from a baseline median of 19 to a median of 2 at month 6 (P < .001), and 73% of patients achieved low disease activity.
Lung involvement stabilized or improved, with 80% of patients showing regression of interstitial changes on high-resolution CT.
A dual-target CD19 (搜索)/BCMA (搜索) chimeric antigen receptor (CAR) T-cell therapy has produced "profound, sustained" remission in patients with refractory systemic sclerosis (搜索) (SSc), according to data presented at the EULAR 2026 Congress. The findings, reported by researchers from Beijing GoBroad Boren Hospital (搜索) in China, suggest that simultaneously targeting CD19 on B-lineage cells and BCMA on plasma cells may offer a transformative approach for patients who have exhausted conventional treatment options.
"Despite advances in immunosuppressive, biologic and antifibrotic therapies, a subset of patients with refractory, progressive systemic sclerosis (搜索) continues to experience uncontrolled skin fibrosis, lung involvement and functional decline," said Yajing Zhang, MD, PhD, of Beijing GoBroad Boren Hospital (搜索), during the presentation. "CD19 (搜索) targeting depletes pathogenic B-lineage cells, whereas BCMA (搜索) targeting may extend immune reset toward plasma-cell-associated autoantibody production, a compartment potentially relevant to refractory SSc."
Study Design and Patient Population
Zhang and colleagues enrolled 11 patients with a median disease duration of 4 years, all of whom had previously received immunosuppression with cyclophosphamide and rituximab. Nine participants had diffuse cutaneous SSc and five had interstitial lung disease at baseline. Following lymphodepletion, all participants received autologous CD19 (搜索)/BCMA (搜索) CAR-T cells at a dose of 1 to 2.2×10⁶/kg. CAR T-cell manufacturing was completed by the GMP Laboratory at Beijing GoBroad Boren Hospital (搜索), with the 19-BCMA vector supplied by Shanghai Take Biotechnology Co. (搜索)
The researchers assessed modified Rodnan Skin Score (mRSS), Health Assessment Questionnaire Disability Index (HAQ-DI), physician and patient global assessments (PGA/PtGA), pulmonary function (FVC/DLCO % predicted), and high-resolution CT at baseline and monthly through month 6 of follow-up.
Rapid and Deep Clinical Responses
All 11 patients demonstrated rapid B-cell aplasia, defined as a CD19 (搜索)+ rate of less than 0.1% via flow cytometry, between day 15 and month 1. The mRSS improved significantly from a baseline median of 19 to a median of 4 at month 3 (P = .002) and further to a median of 2 at month 6 (P < .001). Overall, 73% of participants achieved an mRSS of less than 10, denoting low disease activity.
Functional outcomes also improved markedly. HAQ-DI decreased from 1 to 0.2 (P = .01), while PGA and PtGA declined from 5.5/6 to 1.5/1, respectively (P < .01 for both). Regarding pulmonary involvement, patients demonstrated stabilization or improvement in forced vital capacity and diffusing capacity of the lungs for carbon monoxide. Notably, 80% of patients showed regression of interstitial changes on high-resolution CT.
No disease flares occurred during a median follow-up of 4 months. One patient with overlap syndrome required retreatment but achieved remission following a second infusion.
An Immunological "Reset" with Curative Potential
"Dual-target CD19 (搜索)/BCMA (搜索) CAR-T cell therapy induces profound and sustained clinical remission in refractory systemic sclerosis (搜索)," Zhang stated in a EULAR press release. "By effectively targeting both skin fibrosis and lung progression, this immunological 'reset' strategy offers true curative potential, paving the way for phase 2 trials to redefine the future management of this severe disease."
The concept of deep B-cell depletion driving tissue-level remission in SSc is further supported by a separate proof-of-concept study published in Nature Reviews Rheumatology, in which researchers analyzed sequential skin biopsies from 11 people with diffuse cutaneous SSc before and after anti-CD19 (搜索) CAR T-cell therapy. The findings indicated that anti-CD19 CAR T-cell therapy, which induces deep B-cell depletion, can promote regeneration of fibrotic skin tissue in SSc—a process that has represented a substantial clinical challenge in fibrotic diseases.
Broader CAR T-Cell Advances in Autoimmune Disease
The EULAR 2026 Congress featured multiple presentations highlighting CAR T-cell therapies across autoimmune rheumatic diseases. Fredrik N. Albach, MD, of Charité-University Medicine Berlin, presented data from the phase 1 COMPARE trial evaluating mivocabtagene autoleucel (搜索), a fully human CD19 (搜索)-directed CAR-T cell therapy, in six patients with ACPA-positive, treatment-refractory active rheumatoid arthritis (搜索). The treatment was well tolerated, with mild-to-moderate cytokine release syndrome in three patients and no cases of immune effector cell-associated neurotoxicity syndrome (ICANS). All patients demonstrated decreased disease activity, with three achieving sustained, immunosuppressive-free remission.
Additionally, a novel E-CAR construct incorporating the CD3 cytoplasmic domain to improve signal transduction was presented by Xiaobing Wang, MD, of Shanghai Changzheng Hospital. In a first-in-human pilot study, one patient with SSc demonstrated "dramatic fibrosis reversal and resolution of interstitial lung disease," while three patients with systemic lupus erythematosus (搜索) showed complete clearance of immune complex deposition confirmed by repeated renal biopsies at month 10.
These converging lines of evidence suggest that CAR T-cell therapy is poised to fundamentally alter the treatment paradigm for severe, refractory autoimmune diseases—moving from chronic immunosuppression toward a one-time intervention with disease-modifying and potentially curative outcomes.