New approach to myasthenia gravis: Genetically modified immune cells as a targeted therapy
28.08.2026
CAAR-T cells (Chimeric AutoAntibody Receptor T Cells) represent a promising new treatment approach for neurological autoimmune diseases such as myasthenia gravis. T cells, as an essential component of the immune system, are genetically modified so that they can specifically recognize and destroy autoreactive B cells that are responsible for the development of an autoimmune disease. A team of researchers from Charité — Universitätsmedizin Berlin and the German Center for Neurodegenerative Diseases (DZNE) is working on a corresponding CAAR-T cell therapy, which is supported as part of the SPARK-BIH GCT project funding. The underlying study has now been published in Nature Communications. We spoke with first author Dr. Niels von Wardenburg, physician at the Department of Neurology and Experimental Neurology at Charité and Fellow in the BIH Charité Clinician Scientist Program, about the research findings.
What question did you want to answer, and what were you particularly interested in?
We were primarily interested in whether we could transfer the principle of CAAR-T cell therapy to acetylcholine receptor (AChR)-positive myasthenia gravis (MG). In this rare autoimmune disease, disease-causing antibodies target the acetylcholine receptor, the central docking site on the cell membrane at the neuromuscular synapse through which signals in the nervous system are transmitted. This leads to disruptions in nerve transmission or nerve structure, which can cause symptoms such as visual disturbances and muscle weakness, up to and including respiratory paralysis. Existing therapies often broadly interfere with the protective immune system, making patients more susceptible to infections. They generally have to be administered for life and usually result only in limited disease control. We therefore wanted to develop an approach that was as precise as possible, one that does not attack the entire immune system or all B cells, but instead specifically and very efficiently recognizes and eliminates those B cells that produce disease-relevant autoantibodies against the AChR.
What specific challenges did you encounter in developing your approach?
A key challenge was incorporating the AChR into the T cells in such a way that it could still be recognized by the disease-causing antibodies while at the same time remaining stable on the surface of the T cells. The AChR is a complex receptor consisting of several subunits, and the disease-relevant autoantibodies recognize different regions of this protein. It was therefore important to develop an approach that could cover as many of these disease-relevant autoantibodies as possible.
Another challenge was making the activation of the T cells sufficiently specific: they should react to autoreactive B cells, but not to healthy cells. Our results show that AChR-CAAR-T cells can be specifically activated and can efficiently eliminate disease-relevant B cells.
What surprised you, and why? What was new?
What was particularly interesting to us was that we were able to specifically recognize several disease-causing antibodies at the same time. To achieve this, we combined different variants of the CAAR receptor containing different components of the AChR (α1 and β1). This allowed us to capture a broader spectrum of the antibodies that play an important role in the disease.
What is particularly novel is the idea of not simply eliminating as many B cells as possible, but instead programming the T cells on the basis of the disease-causing autoantibody itself. In a sense, the CAAR-T cells use the target of the autoimmune reaction as “bait”: B cells with matching B-cell receptors are recognized and subsequently eliminated by the T cells. In our preclinical models, this led to a reduction in the corresponding autoantibodies – both in the blood and at the neuromuscular synapse.
What significance could this success have for patients in the future?
If this approach proves to be safe and effective in clinical trials, it could enable a new form of treatment for patients with AChR-positive myasthenia gravis in the long term. The particular hope is to treat the cause of the autoimmune reaction in a more targeted manner rather than suppressing the immune system as a whole.
In the future, this could mean that disease-causing B cells are removed in the long term and that the disease-relevant autoantibodies consequently also decline. In the best-case scenario, this could result in longer-lasting disease control or even a symptom-free state without ongoing therapy. At present, however, this is still a scientific prospect and must first be demonstrated in clinical trials in humans.
Where do you see the translational bridge between research and application?
For us, the translational bridge lies in the fact that we were able to functionally test a concept that was initially developed at the molecular and cellular level in preclinical models. We were able to show that the developed T cells recognize and eliminate disease-relevant B cells and that this can reduce the concentration of the corresponding autoantibodies.
We are currently working to translate these findings toward clinical development. An important next step is the production of AChR-CAAR-T cells according to Good Manufacturing Practice (GMP) quality criteria in order to establish the prerequisites for subsequent clinical testing. The necessary funding for this is available to us through SPARK-BIH project funding as part of the national strategy for gene- and cell-based therapies. This now enables us to specifically prepare the necessary steps on the path from preclinical development to clinical application. If this development is successful, CAAR-T technology could serve as an example of how findings from basic research can be translated into a highly specific immunotherapy for autoimmune diseases.
Original Publication: Bispecific chimeric autoantibody receptor T cells eliminate acetylcholine receptor-specific B cells in myasthenia gravis models