Results of the largest study in the world on the effectiveness of CAR-T cells in treating autoimmune diseases have now been published.
For many people with severe autoimmune diseases, everyday life is marked by pain, exhaustion and taking medication in the long term. Diseases such as systemic lupus erythematosus, systemic sclerosis or autoimmune inflammatory muscle disease are usually lifelong conditions. The results of what is so far the largest study in the world on treating autoimmune diseases with CAR-T cells, the CASTLE study conducted at Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), now give reason for hope. They have demonstrated that a single infusion of CD19 CAR-T cells is sufficient to stop these autoimmune diseases, without the need for any further medication. The researchers have now published the results of the CASTLE study in the journal Nature Medicine.*
“A number of our patients have already been suffering for a long time and have not responded sufficiently to a number of previous treatments,” explains Dr. Melanie Hagen, senior physician and head of the research clinic at Department of Medicine 3 – Rheumatology and Immunology at Uniklinikum Erlangen. “The fact that we are seeing that the disease is calming down considerably after just one treatment is quite unprecedented, both for the patients and for us, the physicians treating them.”
Success through interdisciplinary collaboration
The CASTLE study is an example of what is known as a basket study, in which patients with different autoimmune diseases are treated with CAR-T cells at the same time. The study was conducted in collaboration between Department of Medicine 3 – Rheumatology and Immunology and Department of Medicine 5 – Hematology and Oncology, and succeeded in bringing 24 severely ill patients who had ceased responding to any treatments before the CAR-T cell treatment into a sustained period of remission, without need for any further treatment. “This study clearly indicates how findings from cancer medicine can benefit other groups of patients as well,” explains Prof. Dr. Fabian Müller, senior physician and head of the CAR-T cell unit at Department of Medicine 5. “Close collaboration between the various disciplines was a crucial factor that contributed to the great success of this innovative treatment.”
Own cells transformed into living medicine
In the CASTLE study, certain immune cells, known as T-lymphocytes, were isolated from the patients’ blood and equipped with a chimeric antigen receptor (CAR) outside the patient’s body. After they are returned to the patient’s body, these CAR-T cells recognize other immune cells in the body that are involved in the autoimmune disease and kill them. “The principle of CAR-T cell therapy has been well-established as a treatment for leukemia and lymphatic cancer for several years now. As cells act as medicine, we can also refer to this as a living medicine,” says Prof. Dr. Mackensen, director of Department of Medicine 5 – Hematology and Oncology.
One single infusion instead of a lifetime taking immunosuppressive drugs
The patients continued to experience the positive effects even one year after treatment with CAR-T cells, without them having to resort to taking cortisone or other immunosuppressive drugs. “Our aim is to move away from a lifelong suppression of the immune system,” explains Prof. Dr. Georg Schett, head of Department of Medicine 3 at Uniklinikum Erlangen. “CAR T-cell therapy is the first approach that involves deliberately reprogramming the immune system in the case of severe autoimmune diseases, with the prospect of actually curing these severe diseases. For many patients, this development is a ray of hope – for more energy in their day to day lives, fewer drugs and a better quality of life.”
What are CAR-T cells?
For this cell-based immune therapy, immune cells from the patient’s body (T-lymphocytes) are taken from their blood and genetically modified to allow them to recognize the surface molecule CD19. CD19 is typical for B-lymphocytes, and these are the cells that malfunction in a number of autoimmune diseases. Originally this technology was developed for patients with malignant diseases of B cells (lymphoma). In the meantime, studies have shown that CAR-T cells can also be effective in treating certain autoimmune diseases. The special advantage: The modified CAR-T cells penetrate deep into the affected tissue and permanently switch off the “defective” autoreactive B cells. The defective B cells are then replaced progressively by newly formed, healthy cells. This opens up the door to a whole new approach for treating patients with severe autoimmune diseases that were considered incurable until now.
*DOI: https://doi.org/10.1038/s41591-025-04185-6
Further information:
Dr. Melanie Hagen
Department of Medicine 3 – Rheumatology and Immunology
Phone: + 49 9131/85-39109
melanie.hagen@uk-erlangen.de
Prof. Dr. Fabian Müller
Department of Medicine 5 – Hematology and Oncology
Phone: + 49 9131/85-35956
fabian.mueller@uk-erlangen.de