神经系统疾病的 CAR-T 细胞治疗：科学依据与机制见解

The development and successful clinical application of engineered T cells expressing synthetic chimeric antigen receptors (CARs) represents a milestone in cancer therapy. This approach optimizes physiological in vivo T-cell activation against specific target antigens expressed on defined cell subsets with the goal of their deep and sustained depletion. Significant progress has been made in redesigning CAR T-cell constructs to improve patient safety, therapeutic efficacy, and accessibility. Efforts have also focused on streamlining manufacturing to improve availability and reduce costs, two critical challenges to widespread adoption. Beyond hematologic malignancies, CAR T-cell therapies are now increasingly being repurposed to tackle B-cell-mediated autoimmune diseases (AIDs). This is primarily achieved through broad B-cell depletion, but more targeted approaches-such as the selective elimination of autoantibody-producing B-cell subpopulations-are also being explored. Important considerations in their implementation are identifying the most pertinent patient groups, tailoring their treatment up to the point of CAR-infusion, and following up on their unique toxicity-profile.

In the context of neurological AIDs-including refractory myasthenia gravis, Lambert-Eaton syndrome, multiple sclerosis, and stiff-person syndrome-early clinical experience suggests promising efficacy and tolerability, leading to a growing number of registered clinical trials. In this review, we provide an overview of the mechanism and evolution of CAR T-cell therapy, highlighting why its application in AIDs, particularly in neurology, represents a highly promising therapeutic strategy. How CAR T-cell therapy could help treat neurological disorders CAR T-cell therapy has revolutionized cancer treatment by engineering a patient s own immune cells to recognize and destroy harmful cells.

Initially developed for blood cancers, this therapy is now being explored for autoimmune diseases, particularly neurological disorders like multiple sclerosis, myasthenia gravis, and stiff-person syndrome. The main way CAR T-cells work in autoimmune diseases is by targeting and eliminating B cells, which play a key role in driving these conditions.

Unlike traditional treatments, which often require continuous medication, CAR T-cell therapy has the potential to reset the immune system with long-lasting effects. Early clinical experiences have been promising, showing that CAR T-cell therapy can lead to deep and sustained disease remission.

Importantly, the therapy appears to be well tolerated, with fewer severe side effects than in cancer patients. Research is now focusing on optimizing safety, accessibility, and effectiveness to bring this innovative therapy to more patients. By learning from cancer immunotherapy, scientists aim to refine CAR T-cell treatment for neurological autoimmune diseases, potentially offering a transformative new option for patients who have not responded to conventional therapies.