Chimeric antigen receptor (CAR) T cells have risen as a potent therapeutic weapon against cancer, notably enhancing the management of hematologic neoplasms by specifically targeting malignant B cells. The CD19 antigen found in B cell-related cancers like lymphoma and leukemia marked a significant breakthrough in cancer immunotherapy with autologous CAR T cells. Presently, a number of CAR T cell therapies are authorized and utilized for cancer immunotherapy, targeting either CD19 or B cell maturation antigen (BCMA). Encouraged by these achievements in cancer treatment, research on CAR T cells has expanded beyond cancer to explore their potential in other diseases. Currently, the most notable progress in applying CAR T cells against non-malignant diseases is in the realm of autoimmune disorders.
The pursuit of long-term remission in treating autoimmune diseases poses ongoing challenges. Present intervention methods struggle to effectively manage the root autoimmune mechanism and rely on prolonged administration of immunosuppressive drugs. CAR T cells offer promise in addressing this challenge by profoundly reducing B cell populations through the specific targeting of CD19 or BCMA, present across a broad range of B cells and plasmablasts.
In the neuromuscular field encouraging results come from small case series of patients with myasthenia, LEMS and idiopathic inflammatory myositis (IIM).
In 3 IIM patients with Jo-1 or PL-7 Antibodies CAR T cells reached peak concentrations after a mean of 8.6±0.8 days. CD19+ B cells were rapidly eliminated from peripheral blood after a mean of 5.9±2.2 days. All patients had an ACR–EULAR major clinical response and normalization of creatine kinase levels after 3 months and maintained these responses. Muscular function as measured by MMT-8 normalized in all three patients, and extramuscular disease activity ceased.
In one of the most recently published case reports on MG, 2 patients with highly therapy-refractory MG/LEMS experienced after CAR T-cell therapy sustained clinical recovery, including early gain of muscle strength with achievement of full mobility. QMG scores improved for both patients, decreasing from 21 to 5 points in patient 1 and from 21 to 5 points in patient 2. In parallel, significant improvements in quality of life and activities of daily living were observed in both patients, as assessed by MG-ADL scores.
No severe cytokine release syndrome was reported in these cases.
These data provide evidence for the feasibility, preliminary efficacy, and side-effect profile of CD19 CAR T-cell therapy in patients with severe autoimmune disease. These promising results will need to be confirmed through larger clinical studies. Further studies are also required to identify the optimal target for CAR T cells (e.g., CD19, CD20, BCMA, or others, depending on disease and autoimmune status) in different autoimmune diseases
Key Points:
- CAR T-cells Therapy represent a new promising therapy for autoimmun neuromuscular dieseases as myasthenia and myositis
- First case Reports showed promising results
- Larger clinical studies to better evaluate efficacy and tolerability are needed
References:
- N Engl J Med 2024 Feb 22;390(8):687-700. doi: 10.1056/NEJMoa2308917. CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up Fabian Müller 1, Jule Taubmann 1, Laura Bucci 1, Artur Wilhelm 1, Christina Bergmann 1, Simon Völkl 1, Michael Aigner 1, Tobias Rothe 1, Ioanna Minopoulou 1, Carlo Tur 1, Johannes Knitza 1, Soraya Kharboutli 1, Sascha Kretschmann 1, Ingrid Vasova 1, Silvia Spoerl 1, Hannah Reimann 1, Luis Munoz 1, Roman G Gerlach 1, Simon Schäfer 1, Ricardo Grieshaber-Bouyer 1, Anne-Sophie Korganow 1, Dominique Farge-Bancel 1, Dimitrios Mougiakakos 1, Aline Bozec 1, Thomas Winkler 1, Gerhard Krönke 1, Andreas Mackensen 1, Georg Schett 1
- Neuron 2024 Apr 25:S0896-6273(24)00275-7. doi: 10.1016/j.neuron.2024.04.014. Treatment of concomitant myasthenia gravis and Lambert-Eaton myasthenic syndrome with autologous CD19-targeted CAR T cells. Jeremias Motte 1, Melissa Sgodzai 1, Christiane Schneider-Gold 1, Nina Steckel 2, Thomas Mika 2, Tobias Hegelmaier 3, Dominic Borie 4, Aiden Haghikia 3, Dimitrios Mougiakakos 5, Roland Schroers 6, Ralf Gold 7
- Lancet Neurol 2023 Dec;22(12):1104-1105. doi: 10.1016/S1474-4422(23)00375-7. Anti-CD19 CAR T cells for refractory myasthenia gravis Aiden Haghikia 1, Tobias Hegelmaier 2, Denise Wolleschak 3, Martin Böttcher 3, Christiane Desel 2, Dominic Borie 4, Jeremias Motte 5, Georg Schett 6, Roland Schroers 7, Ralf Gold 5, Dimitrios Mougiakakos 3
Publish on behalf of the Scientific Panel on Muscle and NMJ disorders