CAR T cell therapy shows promise in severe autoimmune neuropathies

In 2 patients with severe, refractory autoimmune neuropathies, autologous anti-CD19 chimeric antigen receptor (CAR) T cell-based therapy induced effective B-cell depletion, antibody reduction, and nerve function recovery. This resulted in rapid and sustained clinical improvement, even without the need for ongoing immunotherapies.

Prof. Jeremias Motte (Ruhr-Universität Bochum, Germany) presented what he described as “two very exciting cases” of successful autologous anti-CD19 CAR T cell therapy in severe autoimmune neuropathies [1,2]. He said B cells drive inflammation and axonal degeneration in autoimmune neuropathies. Ongoing inflammation results in progressive axonal degeneration, loss of neuronal structure and axonal reserve. “Therapies like rituximab also induce B cell depletion, but anti-CD19 CAR T cell-mediated B cell depletion offers distinct advantages,” Prof. Motte explained. CAR T cells are effective against all systemic B cells and CD19 plasmablasts, and induce deep, broad depletion, 'rebooting’ the B cell compartment and exerting a sustained effect. CAR T cells may be a treatment option for chronic autoimmune neuropathies with a severe disease course, particularly in cases where anti-neonatal Fc receptor (FcRn) antibodies or complement neutralisation are not effective.

Prof. Motte presented 2 cases involving patients with a history of more than 12 months of severe tetraparesis and insufficient response to established immunotherapies: a 72-year-old man with GM1 antibody motor variant of CIDP and a 54-year-old man with NF155 antibody paranodopathy [2]. Leukapheresis, lymphodepletion, and CAR T cell administration were performed under a standardised protocol. The patients' clinical symptoms began improving within 4 weeks after CAR T cell transfer, and they continued to improve thereafter. In both cases, all immunotherapy was discontinued. After 6 months, one patient was able to perform squats and pull-ups, while the other patient could walk independently over 200 meters. These improvements were also reflected in conventional parameters like the Inflammatory Neuropathy Cause and Treatment-Overall Disability Sum Score (INCAT-ODSS), muscle strength, and grip strength. Side effects were generally moderate; one patient had hypogammaglobulinaemia, requiring periodic immunoglobulin replacement.

Prof. Motte concluded: “In our department, we have now treated 11 patients with severe disease using CAR T cell therapy. We observed that treating early makes the therapy very effective, so do not wait too long.”

1. Motte J, et al. Persistent remission from treatment refractory autoimmune neuropathies by autologous CD19-targeted CAR T cell therapy. SPS09_4, EAN Congress 2025, 21-24 June, Helsinki, Finland.
2. Motte J, et al. Lancet Neurol. 2025;24(7):564-566.

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Posted on 3 September 2025