Lectures and seminars OnkPat Friday Seminar: CAR T Cell Therapy: From Lymphoma to Autoimmunity

Host: Maurice Michel, Department of Oncology-Pathology

Biosketch

Dimitrios Mougiakakos (46) began his academic career in 1998 with a degree in human medicine at the Hannover Medical School, which he completed in 2005. His specialist training in hematology and oncology took him to Freiburg, Regensburg and Erlangen. Between 2008 and 2011, he continued his research at the Karolinska Institute, supported by the German Research Foundation (DFG). After returning to Germany, Mougiakakos took over a Max Eder junior research group, funded by German Cancer Aid, and completed his habilitation at the Friedrich-Alexander University in Erlangen. In 2017, he was awarded a W2 professorship (associate professor) for tumor immunology and moved to the Otto-von-Guericke University in Magdeburg as chair (full professor) and director of the Department of Hematology, Oncology and Cell Therapy at the end of 2021. 

His research focuses on tumor immunology and in particular on cell-based approaches in immunotherapy. He was instrumental in the world's first treatment of systemic lupus erythematosus, myasthenia gravis and primary immune thrombocytopenia with CD19 CAR T cells. He has published more than 180 papers, including in the Lancet, Lancet Neurology, New England Journal of Medicine, Nature and Nature Medicine, and has received more than €25 million in grant funding.

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has recently been extended from hematologic malignancies to the treatment of severe, refractory autoimmune disorders, representing a fundamental shift from chronic immunosuppression toward immune reprogramming. Early clinical applications have demonstrated that targeted elimination of autoreactive immune compartments can induce profound and durable disease control in patients with otherwise therapy-resistant autoimmune diseases. The mechanistic rationale of CAR T-cell therapy in autoimmunity is closely linked to the pleiotropic role of B cells in immune dysregulation. Beyond autoantibody production, B cells contribute to antigen presentation, cytokine secretion, and the modulation of pathogenic T-cell responses. B-cell–directed cellular therapy therefore addresses multiple immunopathogenic pathways simultaneously and provides a biological basis for sustained disease remission. 

Clinical experience initially obtained in rheumatologic autoimmune diseases has expanded to neurological disorders and selected benign hematologic conditions. Accumulating evidence indicates that CAR T-cell therapy can induce long-lasting, therapy-free remissions, accompanied by a reconstitution of the immune system that differs fundamentally from conventional immunosuppressive strategies. These observations have given rise to the concept of an immunological “reset,” characterized by the restoration of immune tolerance rather than transient disease suppression. 

Key aspects of clinical implementation include careful patient selection, standardized lymphodepleting conditioning, close monitoring, and structured management of treatment-related toxicities. Available data suggest a distinct safety profile in autoimmune indications, with generally lower incidence and severity of cytokine release syndrome and neurotoxicity compared with hematologic malignancies. Ongoing developments focus on improving accessibility, scalability, and efficacy of cellular immunotherapy in autoimmunity. Emerging approaches such as antigen-specific repolarization of polyclonal T cells without genetic modification, as well as next-generation platforms including allogeneic and in vivo CAR strategies, are expected to further expand the therapeutic landscape.

Recent publications

BCMA-CD3 T-cell engager as salvage therapy for multirefractory primary immune thrombocytopenia.
Duque-Afonso J, Rummelt C, Förster K, Zeiser R, Mougiakakos D
Lancet 2026 Jan;407(10527):489-491

Effective use of BCMA-targeting bispecific T cell-engaging antibody in treatment-refractory LRP4+ myasthenia gravis.
Schreiber S, Al-Dubai M, Vielhaber S, Lefterova L, Dietrich S, Ruck T, Meuth S, Walther D, Mougiakakos D
Mol Ther 2025 Sep;33(9):4130-4134

Salvage treatment of multi-refractory primary immune thrombocytopenia with CD19 CAR T cells.
Trautmann-Grill K, von Bonin M, Georgi A, Middeke JM, Böttcher M, Meyer O, Borie D, Bornhäuser M, Mikusko M, Wolleschak D, Mougiakakos D
Lancet 2025 Jan;405(10472):25-28

CAR T cells in autoimmunity: game changer or stepping stone?
Mougiakakos D, Meyer EH, Schett G
Blood 2025 Apr;145(17):1841-1849

Clinical efficacy and autoantibody seroconversion with CD19-CAR T cell therapy in a patient with rheumatoid arthritis and coexisting myasthenia gravis.
Haghikia A, Hegelmaier T, Wolleschak D, Böttcher M, Pappa V, Motte J, Borie D, Gold R, Feist E, Schett G, Mougiakakos D
Ann Rheum Dis 2024 Oct;83(11):1597-1598

B cell-targeting chimeric antigen receptor T cells as an emerging therapy in neuroimmunological diseases.
Haghikia A, Schett G, Mougiakakos D
Lancet Neurol 2024 Jun;23(6):615-624

CAR T-cell therapy in autoimmune diseases.
Schett G, Mackensen A, Mougiakakos D
Lancet 2023 Nov;402(10416):2034-2044

Anti-CD19 CAR T cells for refractory myasthenia gravis.
Haghikia A, Hegelmaier T, Wolleschak D, Böttcher M, Desel C, Borie D, Motte J, Schett G, Schroers R, Gold R, Mougiakakos D
Lancet Neurol 2023 Dec;22(12):1104-1105

CD19-Targeted CAR T Cells in Refractory Systemic Lupus Erythematosus.
Mougiakakos D, Krönke G, Völkl S, Kretschmann S, Aigner M, Kharboutli S, Böltz S, Manger B, Mackensen A, Schett G
N Engl J Med 2021 Aug;385(6):567-569