A team of physicians at the German Center for Immunotherapy at Erlangen University Hospital has succeeded for the first time worldwide in successfully treating a 21-year-old female patient with therapy-resistant, severe chronic inflammatory bowel disease (ulcerative colitis) using cell therapy with CD19 CAR-T cells.
The 21-year-old patient had been suffering from highly active Colitis ulcerosa for five years and was no longer responding to any of the available medications, including various targeted biologics and JAK inhibitors. The young woman's quality of life was significantly impaired, and with several episodes of bloody diarrhea and recurring abdominal pain throughout the day, everyday tasks were stressful, working was virtually impossible, and even visits to the Center for Chronic Inflammatory Bowel Diseases at Erlangen University Hospital were difficult.
After CAR-T cell therapy, the diarrhea and abdominal pain disappeared completely, colonoscopies showed complete healing of the previously inflamed intestinal mucosa, and body weight rose to a healthy normal level within a few months. For the first time in years, the patient is able to live a normal life again.
For this cell-based immunotherapy, the patient's own immune cells (T lymphocytes) are taken from the blood and genetically modified to recognize the surface molecule CD19. CD19 is characteristic of B lymphocytes, which are malfunctioning in many autoimmune diseases. This technology was originally developed for patients with malignant B-cell diseases (lymph node cancer). Studies have now shown that CAR-T cells can also be effective in certain autoimmune diseases.
The particular advantage is that the modified CAR-T cells penetrate deep into the affected tissue and permanently switch off the “diseased” autoreactive B cells. The diseased B cells are then replaced by healthy, functional cells. This opens up a completely new treatment approach for patients with severe autoimmune diseases that were previously considered incurable.
This world-first use of CD19 CAR-T cells in ulcerative Colitis shows that even in diseases where the role of misdirected B cells as a cause was unclear, a complete response with subsequent freedom from medication is possible. “The results are very promising and give cause for great hope for those affected,” said Prof. Dr. Fabian Müller, head of the CAR-T Cell Unit at Medical Clinic 5. “The results are very promising and give cause for great hope for those affected,” said Prof. Dr. Fabian Müller, head of the CAR-T cell unit at Medical Clinic 5.
Treatment with CAR-T cells at the German Center for Immunotherapy was carried out through interdisciplinary collaboration between various departments of Medical Clinic 1 at Erlangen University Hospital: Gastroenterology, Pneumology, and Endocrinology (Director: Prof. Dr. Markus F. Neurath) and Medical Clinic 5 – Hematology and Internal Oncology (Director: Prof. Dr. Andreas Mackensen) in close cooperation with Medical Clinic 3 – Rheumatology and Immunology (Director: Prof. Dr. med. univ. Georg Schett). The production of the CAR-T cells was carried out in a specialized clean room laboratory at Medical Clinic 5 under the direction of PD Dr. Michael Aigner.
The results were published in the New England Journal of Medicine.