Chimeric antigen receptor (CAR) T-cell therapy appears safe, decreases relapse rates, and improves functionality and quality of life in patients with neuromyelitis optica spectrum disorder (NMOSD), according to a recently published study in Signal Transduction and Targeted Therapy.

The pathophysiology of NMOSD involves antiaquaporin 4 (AQUP4) antibodies that bind to AQUP in the optic nerve and spinal cord, unleashing an autoimmune response that leads to numerous neurological deficits. Currently, oral immunosuppressants constitute the mainstay of therapy; however, up to 60% of patients receiving oral treatment experience recurrent episodes.

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The use of monoclonal antibodies to target the CD20 antigen in B cells turned out to be ineffective in many patients and did not significantly decrease anti-AQUP4 antibodies. Therefore, there is a need for therapy that directly targets AQUP4- IgG-producing cells.

CAR-T cell therapy has already been successfully used to treat hematologic malignancies and autoimmune diseases like systemic lupus erythematosus. Therefore, the authors aimed to assess the efficacy of CAR-T cell therapy targeting the B-cell maturation antigen (BCMA) present in resident plasma cells of the central nervous system. 

Although BCMA-targeted CAR-T cell therapy has already been tested in the context of multiple myeloma, this is the first study using it in autoimmune disease, the authors noted.

The single-arm phase 1 clinical trial included 12 patients with AQUP4-IgG seropositive NMOSD, of which 10 were women with a median age of 49 years. All patients had a history of recurring attacks despite using several immunosuppressing therapies, with a median of 2 attacks per patient.

All patients experienced grade 3 adverse effects, with blood toxicity being the most common; however, most adverse effects were resolved within 4 weeks after infusion.

Serum AQUP4 levels decreased in all patients after infusion and were negative in 7 patients 12 weeks after infusion. Although BCMA levels significantly decreased 1-month post-infusion, they returned to baseline levels after 6 months.

After a median follow-up of 5.5 months, 92% of patients achieved drug-free remission. According to the Expanded Disability Status Scale, all patients had a significant improvement in functionality, with either corrected visual acuity or improvements in ambulation.

“In this ongoing phase 1, first-in-human clinical study of CT103A, CAR T-cell therapy targeting BCMA, in relapsed or refractory AQP4-IgG seropositive NMOSD, patients displayed a manageable safety profile and had a promising clinical response without any additional immunosuppressive therapy,” the authors concluded.


Qin, C., Tian, DS., Zhou, LQ, et al. Anti-BCMA CAR T-cell therapy CT103A in relapsed or refractory AQP4-IgG seropositive neuromyelitis optica spectrum disorders: phase 1 trial interim results. Sig Transduct Target Ther. Published online January 4, 2023. doi:10.1038/s41392-022-01278-3