Novel CAR T-Cell Therapy to Combat Myositis

Universitätsklinikum Erlangen is the first in the world to use chimeric antigen receptor (CAR) T cells to successfully treat a patient suffering from severe myositis. The disease is triggered by a malfunction in the immune system that leads to inflammation of the muscles, and the risk of developing a very severe form of the disease is high. The Lancet has now published news of the successful treatment in a case report.

When the 41-year-old Mr. S. noticed a dramatic deterioration in his health last year, he initially put it down to a viral infection. However, things worsened when he was suddenly no longer to move more than a few feet and was barely able to stand up. His symptoms were caused by a severe autoimmune disease affecting his muscles, joints, skin, and lungs belonging to the group of autoimmune muscle inflammatory diseases (myositis). He was diagnosed with anti-synthetase syndrome.

The name anti-synthetase syndrome is derived from the observation that the enzymes required for the synthesis of amino acids known as aminoacyl-tRNA synthetases are erroneously attacked by the immune system. This severely impacts the function of various cells.

Modifying patients’ own immune cells: hope for the future

“Autoimmune inflammatory muscle diseases are severe diseases that can end fatally if they are diagnosed at too late a stage or patients fail to react sufficiently to medicines aimed at suppressing the immune system,” says Georg Schett, MD, professor, and director of the Department of Medicine 3–Rheumatology and Immunology at Universitätsklinikum Erlangen.

In the case of Mr. S., all traditional treatments used to suppress the immune system failed, but he was saved by CD19-targeted CAR T cells. “CAR T cells are immune cells withdrawn from the patient’s blood and genetically engineered to carry a chimeric antigen receptor (CAR),” says Dr. Andreas Mackensen, professor, director of the Department of Medicine 5–Hematology and Oncology. “Once the cells are returned to the patient’s body, the CAR allows the modified immune cells to specifically target the cells triggering the disease.”

Complete recovery after six months

After receiving the infusion of CAR T cells, Mr. S. experienced a dramatic improvement in his health: the inflammation in his muscles, lungs, and joints relapsed almost entirely and so did his strength, performance, and stamina. “What was particularly surprising was that Mr. S. was able to stop taking all immune-suppressive medicine and in particular corticosteroids without the disease flaring up again,” said Fabian Müller, MD, Department of Medicine 5, who is caring for the patient. Six months after receiving the CAR T cells, Mr. S. has recovered entirely from his autoimmune disease.

“It acted like pressing a reset button! Before treatment, I could do nothing, and now I’m functioning like normal again,” says Mr. S. This is the second type of autoimmune disease that clinicians at the Deutsches Zentrum Immuntherapie (DZI), Universitätsklinikum Erlangen have successfully treated using CAR T cells. In the first instance, the cells excelled in treating systemic lupus erythematosus (SLE).

Funding for the research led by professors Schett and Mackensen is provided by Collaborative Research Centers 1181 and 221 of the German Research Foundation, the High-tech Agenda of the Free State of Bavaria, and the 4I Immunocluster Erlangen-Regensburg-Würzburg. Other patients dealing with myositis or SLE will be offered the opportunity of benefiting from CAR T-cell treatment as part of the clinical CASTLE study, starting this year.

- This press release was originally published on the Friedrich-Alexander-Universität Erlangen-Nürnberg website