Safety and clinical activity of autologous RNA chimeric antigen receptor T-cell therapy in myasthenia gravis

Myasthenia gravis (MG) is a prototypical neuroimmunological disorder in which autoantibodies targeting the neuromuscular junction play a key role in the pathogenesis. Granit et Al. reported the results of a prospective, multicenter, open-label, phase 1b/2a study that investigated the safety and efficacy of Descartes-08, a chimeric B-cell antigen receptor anti-maturating antigen (BCMA) T-cell therapy, in patients with generalized MG. The interesting RNA-based CAR T-cell approach avoids potentially harmful lymphodepletion chemotherapy. Infusions of Descartes-08 in different dose patterns were well tolerated and not associated with the adverse effects typical of DNA-based CAR T cell therapies, such as cytokine release syndrome. Most study participants showed clinically significant improvements in MG disease severity score that persisted for months. This preliminary study, which showed encouraging results, may open new avenues for the exploration of rCAR-T as a therapeutic approach for neuroimmunological disorders, but will need to be confirmed by larger double-blind studies.