Cellular therapies in autoimmune neuromuscular disorders: the new frontier

Antibody-mediated humoral immunity plays a vital role in a number of autoimmune neuromuscular disorders (AINMD), such as myasthenia gravis, Lambert-Eaton myasthenic syndrome (LEMS), stiff-person syndrome (SPS), and autoimmune myositides. Although biologics based B cell and plasma cell depletion (BCDT) therapy effectively treats some AINMDs, its variable success highlights the limitations of this therapeutic modality. B cell directed cellular therapy (BCDcT) targeting a wide array of B cell lineages, including short-lived plasma cells, has emerged as an effective treatment modality in hematological malignancies, resulting in impressive reductions in tumor burden, relapse rates, and mortality. Despite the impressive success of BCDcT, especially in hematological malignancies, its initial use was limited to last-resort cases due to the high morbidity associated with cytokine release syndrome (CRS) and immune cell-associated neurological toxicity (ICANS). Recent improvements in the safety profile of BCDcTs and better clinical management have lowered the incidences of CRS and ICANS, leading to its earlier use in some cancers. The success of BCDcT in B cell malignancies has promoted strong interest in applying this therapeutic approach to autoimmune disorders, particularly AINMD. This review will cover cell therapy fundamentals, limitations of current BCDTs, experiences with cell therapy in AINMD, and both ongoing and planned trials in this field.