新鲜制剂 CD19 CAR-T 细胞成功治疗 GAD65 抗体介导的小脑性共济失调：一例病例报告

Chimeric antigen receptor T (CAR-T) cell therapy is an effective treatment for treatment-refractory hematological disorders with an acceptable safety profile. In contrast, preliminary reports suggest good efficacy for treatment-refractory autoimmune disorders, including autoimmune nervous system disease, but their safety profile is largely unknown.

To describe the first case of glutamic acid decarboxylase-65 (GAD65) antibody-mediated cerebellar ataxia (CA) successfully treated with CD19 CAR-T cells.

A 33-year-old male was diagnosed with GAD65 antibody mediated CA in 2023. Despite treatment with Rituximab and Cyclophosphamide, the patient's condition worsened with new-onset recurrent falls and increasing vertigo. Ambulation was maintained. CD19 CAR-T cells at a dose of 1 10 6 cells per kilogram of body weight were infused after administration of standard lymphodepleting chemotherapy, resulting in a good serological response with reduction of GAD65 serum titers by 95% at day +90, significant clinical improvement in ataxia at day +30 and no evidence of disease progression at day +270 clinically, radiologically and laboratory-wise. The toxicity was limited to cytokine release syndrome grade 1. DISCUSSION: The favorable clinical response observed in our patient, along with other reports demonstrating preliminary efficacy and limited toxicity, supports further study of CD19 CAR-T cell therapy in GAD65 neurological disorders.