CAR-T cell therapy treats severe bowel disease successfully for the first time

21 year old with therapy-resistant, severe inflammatory bowel disease treated successfully with cellular immune therapy

A team of doctors from Deutsches Zentrum Immuntherapie at Uniklinikum Erlangen has succeeded for the first time in treating a young patient with a severe case of therapy-resistant inflammatory bowel disease (ulcerative colitis) with cell therapy using CD19-CAR-T cells. The results of this innovative treatment have been published in the latest issue of the New England Journal of Medicine.

A life with severe bowel disease

The 21 year old patient has been suffering from highly active ulcerative colitis for five years now and was no longer responding to any available medication, including various targeted biopharmaceuticals and JAK inhibitors. The disease had a severe impact on the young woman’s quality of life, bloody diarrhea and stomach pain throughout the day made it hard for her to make it through the day at all. Working was virtually out of the question, and even attending doctor’s appointments at the Center for Chronic Inflammatory Bowel Disease at Uniklinikum Erlangen was difficult.

CAR-T cell therapy was a game changer: The diarrhea and stomach ache vanished, colonoscopies revealed that the previously inflamed intestinal lining had healed completely and the patient’s weight rose to a healthy level within a matter of months. The patient has been able to live a normal life again for the first time in years.

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 healthy, functioning cells. This opens up the door to a whole new approach for treating patients with severe autoimmune diseases that were considered incurable until now.

Close collaboration and local production of CAR-T cells at Uniklinikum Erlangen

Treatment using CAR-T cells at the Deutsches Zentrum Immuntherapie was made possible thanks to interdisciplinary collaboration between Department of Medicine 1– Gastroenterology, Pneumology and Endocrinology (director: Prof. Dr. Markus F. Neurath) and Department of Medicine 5 – Hematology and Oncology (director: Prof. Dr. Andreas Mackensen) in close collaboration with Department of Medicine 3 – Rheumatology and Immunology (director: Prof. Dr. med. univ. Georg Schett). The CAR-T cells were produced in a specialized cleanroom at the Department of Medicine 5, supervised by PD Dr. Michael Aigner.

Significance and outlook

This is the first time ever that CD19 CAR-T cells have been used to treat ulcerative colitis anywhere in the world, and it has demonstrated that patients can respond positively and become fully independent of medication even in diseases in which it was unclear to what extent malfunctioning B cells are the cause. “The results are very promising and give patients great cause for hope,” explains Prof. Dr. Fabian Müller, head of the CAR T-cell unit at Department of Medicine 5.

At the same time, Prof. Dr. Raja Atreya, senior physician at Department of Medicine 1, emphasizes: “Until now, this is one isolated case. In order to be able to judge the safety and effectiveness of the therapy, further patients must be treated as part of studies. This is the only way to be able to determine which patients would benefit particularly from this new therapy.”

Further information:

Prof. Dr. Andreas Mackensen
Uniklinikum Erlangen
Phone: +49 9131 85 35954
andreas.mackensen@uk-erlangen.de

Prof. Dr. Markus F. Neurath
Uniklinikum Erlangen
Phone: +49 9131 85 35204
markus.neurath@uk-erlangen.de