Case Report: CD20/BCMA bispecific CAR-T therapy for progressive multiple sclerosis.

Refractory secondary progressive multiple sclerosis (SPMS) remains an area of unmet need, particularly once disability continues to accumulate despite multiple disease-modifying therapies. Two SPMS patients are reported with C-CAR168 treatment, a bispecific CD20/BCMA CAR-T product, achieving 12- and 6-month drug-free remission. Patient 001 (EDSS 4.0→3.0) showed improvement of oculomotor dysfunction, ataxia, and cognitive impairment. Patient 002 (EDSS 6.5→6.0) demonstrated halted lower-limb progression and relieved bowel/bladder dysfunction. C-CAR168 infiltrated into the cerebrospinal fluid (CSF), persistently depleted pathogenic B-lineage cells and CD20dim T cells, and normalized inflammatory markers with an overall favorable safety profile. This first-in-human experience supports bispecific CAR-T as a promising immune-reprogramming strategy for refractory SPMS.