Promising Effects of CAR T-Cell Therapy in Refractory Stiff Person Syndrome and a Hopeful Future for All...

Chimeric antigen receptor (CAR) T cells are genetically modified T cells expressing CARs, initially developed to recognize tumor antigens and kill cancer cells that evade T-cell recognition. Because of their impressive success in hemato-oncologic malignancies, CAR T cells are being repurposed with redesigned constructs for safety and sustained efficacy to target refractory systemic autoimmune or neurologic diseases. The CD19 CAR T cells-targeting those CD19-positive, antibody-secreting, long-lived plasma cells, and plasmablasts-are now extensively explored in refractory neuroautoimmunities with promising benefits based on case series in patients with myasthenia gravis (MG), stiff person syndrome (SPS), neuromyelitis, myositis, and multiple sclerosis; some patients with MG and SPS with steadily progressive and disabling disease refractory to all available therapies, including rituximab and new biologics, exhibit impressive clinical improvements with long-lasting benefits. The review, triggered by these early results and ongoing trials, addresses what these cells are and why they show effectiveness not only in antibody-mediated B-cell neurologic diseases unresponsive to available anti-B-cell agents but also in patients with nonpathogenic antibodies, implying effects even beyond B cells; points out that CARs are "living cells" penetrating physiologic barriers, such as the blood-brain barrier, expanding within tissues to memory cells ensuring sustained effects; describes the process and challenges of preparing and administering CAR T cells and their safety profile stressing the differences in toxicities when treating autoimmunites vs malignancies; and highlights that CD19 CAR T cells can successfully target even 2 different autoimmune diseases in the same patient, such as SPS and MG, offering promising prospects of changing the therapeutic algorithm in all neuroautoimmunities with potential for achieving even an immune reset shifting immunity to a healthy state.