# CAR T-Cell Immunotherapy in Neuroautoimmune Diseases: Focus on the Central Nervous System

## TL;DR

This paper reviews how CAR T-cell therapy, currently used for cancer, might be applied to treat severe autoimmune diseases of the central nervous system.

## Contribution

The paper provides a comprehensive review of CAR T-cell therapy's potential in CNS autoimmunity, including clinical experiences and ongoing trials.

## Key findings

- CAR T-cells may target immune cells in the CNS, offering a novel treatment for severe autoimmune diseases.
- Current clinical trials involve only 15 patients with treatment-refractory CNS autoimmunity.
- Future use of CAR T-cells depends on proving their efficacy, safety, and cost-effectiveness.

## Abstract

The treatment of central nervous system (CNS) autoimmune diseases has evolved from broad immunosuppression toward targeted disease-modifying therapies (DMTs). While current DMTs effectively control inflammatory activity in many patients, unmet needs remain, including persistent compartmentalised CNS pathology, limited tissue penetration, and the cumulative burden of chronic therapy. Chimeric antigen receptor (CAR) T-cell therapy represents a novel “living” immunotherapy capable of antigen-specific cellular depletion. Although currently approved only for B-cell malignancies, CAR T-cells are increasingly being explored in CNS autoimmunity leveraging their capacity for autonomous cytotoxicity and expected access to immune cells within protected CNS niches following a potentially single intervention. In this review, we examine CAR T-cells in the context of CNS-autoimmunity, we outline principles derived from oncologic applications, assess current DMTs, their limitations and side effects, and define parameters where CAR T-cells may offer added value. We discuss biological and practical requirements for broader clinical application, as currently they are investigated only for the very severe and refractory cases where all alternative treatments have failed. We further review the plasticity of CAR constructs, distinguishing clinically advanced platforms from early proof-of-concept approaches. Finally, we summarise clinical experience from 15 patients with CNS autoimmunity treated with CAR T-cells and review ongoing or planned trials that include such patients. We conclude that CAR T-cell therapy remains investigational for severe, treatment-refractory disease, with future applicability dependent on demonstrable efficacy, safety, cost, and feasibility beyond existing DMTs.