Bispecific CAR T-cell therapy yields durable responses in treatment-refractory autoimmune diseases, study shows
Presenter: Nan Shen, MD, PhD, Director, Shanghai Institute of Rheumatology, Renji Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
Anti-CD20/BCMA bispecific CAR-T cell therapy promotes immune reset and sustained drug free remission in refractory autoimmune diseases. Abstract LB04. Presented October 28, 2025.
A novel immunotherapeutic treatment has demonstrated durable responses in treatment-refractory autoimmune diseases, researchers reported at ACR Convergence 2025.
The bispecific chimeric antigen receptor (CAR) T-cell therapy known as C-CAR168 had a favorable safety profile and encouraging efficacy in both lupus nephritis and multiple sclerosis, according to study results presented by Nan Shen, MD, PhD.
Efficacy findings included a high renal response rate in refractory proliferative lupus nephritis, and rapid neurologic improvements in secondary progressive multiple sclerosis.
Those results were achieved without the use of standard-of-care background medications, according to Dr. Shen and co-authors.
That fact, coupled with mechanistic evidence of immune reset, provides a “compelling rationale” for further clinical evaluation of C-CAR168, the authors said in their abstract.
“Refractory autoimmune diseases with progressive organ damage remain a major unmet medical need,” they added.
C-CAR168 is an autologous anti-CD20/BCMA bispecific CAR-T therapy. It is designed to target autoantibody-producing plasma cells and their B-cell precursors simultaneously, aiming for a complete “immune reset,” the authors said.
This first-in-human, phase 1, open-label study involved patients with autoimmune diseases for whom at least two standard immunosuppressive therapies had failed. All patients received a single infusion of C-CAR168 in one of two doses, either 0.75 × 10⁶ or 1.5 × 10⁶ CAR-T cells per kg.
A total of 16 patients were treated. Eleven had systemic lupus erythematosus, of whom nine had lupus nephritis. Of the remaining five patients, two had progressive multiple sclerosis, two had neuromyelitis optica spectrum disorder, and one had immune-mediated necrotizing myositis.
Treatment with C-CAR168 had “robust efficacy” in both the lupus nephritis and secondary progressive multiple sclerosis cohorts, the investigators said.
The nine patients with proliferative lupus nephritis had previously received a median of four immunosuppressive or biologic agents, and seven of them (78%) achieved a renal response, including three patients who had a complete response. Further results indicated rapid improvement in proteinuria at a median of 1 month.
Among the seven patients with lupus nephritis with at least 3 months follow-up, six (86%) had an improvement in extrarenal systemic lupus erythematosus activity, data show.
Of the two patients with secondary progressive multiple sclerosis, one showed significant improvement in gait and orbital movement, the authors said. That patient also had an improved score on the Expanded Disability Status Scale (EDSS), reduced lesion burden on magnetic resonance imaging, and normalized serum neurofilament light chain level.
No dose-limiting toxicities were observed. Adverse events of grade 3 or greater, primarily hematologic, were transient, according to the investigators.
Eleven patients experienced grade 1 or 2 cytokine release syndrome that resolved with supportive care alone, the investigators added. No CAR-T-associated neurotoxicity (ie, immune effector cell-associated neurotoxicity syndrome) was observed.
All 16 patients discontinued their immunosuppressants and biologic agents, and 12 (75%) were able to discontinue corticosteroid treatment, according to the report.
Disclosures
Nan Shen, MD, PhD, reported no disclosures. Co-authors on the study reported employment with AbelZeta.
References
Ding H, Li W, Shen Y, et al. Anti-CD20/BCMA bispecific CAR-T cell therapy promotes immune reset and sustained drug free remission in refractory autoimmune diseases [abstract]. Arthritis Rheumatol 2025; 77 (suppl 9). https://acrabstracts.org/abstract/anti-cd20-bcma-bispecific-car-t-cell-therapy-promotes-immune-reset-and-sustained-drug-free-remission-in-refractory-autoimmune-diseases/. Accessed October 29, 2025.