“You sometimes need courage to work in medicine”

Georg Schett and his groundbreaking treatment

Two years ago, Georg Schett treated patients suffering from serious autoimmune disease using the patients’ own genetically-modified cells for the first time. It was so successful that these patients do not require any other form of treatment.

Prof. Dr. Georg Schett, Director of the Department of Medicine 3 at Universitätsklinikum Erlangen has courage. In 2021, he was the first person to treat a patient with life-threatening systemic lupus erythematosus (SLE) with a treatment known as CAR T-cell therapy. We asked Schett, who was awarded the prestigious Leibniz Prize in 2023, the most important research award in Germany, about the progress of his research.

Prof. Schett, what is CAR T-cell therapy exactly?

During this treatment, immune cells known as T-cells are removed from the patient and equipped with a chimeric antigen receptor (CAR). In the body, the CAR docks onto the immune cells, specifically to B-cells, that mistakenly attack the body’s own tissue. It ensures that the B-cells are destroyed by the genetically-modified T-cells. This triggers a kind of restart of the immune system, which then stops attacking the body’s own structures.

You have since treated other patients with this therapy. Do you know how they are doing?

All 15 patients are doing well. Their condition has either significantly improved or they are cured. And most importantly, they don’t need any further treatment. This is a new development. One treatment with the CAR T-cells was enough.

After this success, you have now started a clinical study for CAR T-cell therapy.

Yes, we have called it the CASTLE study. The study is a CAR T-cell study for three autoimmune diseases: SLE, autoimmune muscle inflammation and systemic sclerosis. 24 seriously ill patients will receive treatment from us during the coming twelve to eighteen months. The list of people who would like to take part is considerably longer. Even before we started the study, we had enough candidates – not least because the data we have to date is very good. It’s interesting to note that patients regard the treatment as a “natural” therapy. This is because it contains their own cells that attack the misguided immune cells.

Are there any side effects?

Every treatment has potential risks. For example, before receiving the CAR T-cells, each patient receives two immunosupressive drugs, but only for a short period: one is administered for one day only and the other for three days. This reduces the number of white blood cells, but only for a period of around one week to ten days. In contrast to leukemia, where CAR T-cell therapy is also used, it is extremely rare for permanent immune deficiency to be triggered as a result. The pretreatment is surprisingly well tolerated. The second risk is that inflammation can occur when the CAR T-cells in the body are activated. This can lead to fever and shock in the worst case. We haven’t had any cases of this yet, though.

You were the first person to use this treatment for autoimmune diseases. How does it feel to be a pioneer in such a field?

We were a bit nervous of course. But it was a case of weighing up the risks and benefits. We saw a good opportunity for improving the patient’s condition. And we put the opportunity to give a young woman a new life above the potential risks involved. In addition, we believed that we would be able to use medication to manage any problems that may arise. Looking back, it was the right thing to do. In the field of medicine, you sometimes need a bit of courage otherwise nothing happens and you just carry on doing the same thing all the time.

Prof. Dr. Georg Schett studied medicine at the University of Innsbruck where he also gained his doctoral degree and worked as a research associate. He became a specialist in internal medicine in 2001 and in 2003 was appointed Assistant Professor for Internal Medicine at the Medical University of Vienna. After a period conducting research at biotech firm Amgen in the USA, Schett was appointed Professor of Internal Medicine and Director of the Department of Medicine 3 at Universitätsklinikum Erlangen in 2006. He is spokesperson of the Infectiology and Immunology Key Research Priority and Vice President Research at FAU. Georg Schett is a member of numerous scientific societies and committees, visiting professor at several universities in the USA and China and has won many prestigious awards. He is one of the world’s most renowned scientists in the field of rheumatology and immunology.

Could you imagine using the treatment one day for other autoimmune diseases such as multiple sclerosis?

B-cells also produce damaging antibodies in multiple sclerosis. It is therefore feasible that patients suffering from MS could benefit from this treatment. The most important thing for autoimmune diseases is not to start treatment too late, however, because damage that has already been caused cannot be repaired. MS destroys nerve cells that cannot be regenerated. This means the timing of the treatment is important. I think it’s likely that we will be treating a patient suffering from MS or myasthenia gravis using CAR T-cell therapy during the next few months. We just have to try it and see what happens.

Will CAR T-cell therapy remain a treatment option for patients who are seriously ill where established treatments don’t work and where it means preventing further damage?

Initially, yes as these patients have their backs to the wall. During a second stage, it could be used on patients where we can predict severe cases early on to prevent the disease from going completely out of control.

You have specialized in inflammatory diseases and have made other discoveries in this field. What drives you the most and what are you most interested in?

Gaining a better understanding of inflammation and providing better treatment is what spurs me on. I’m also always interested in new things. That’s what I love about research – you can always discover something new. I’m particularly fascinated by CAR T-cell therapy as the effects for patients are immediately visible. We have started something that will now be taken up by other countries and will probably help many people. That’s something you don’t experience every day. I’m grateful that it’s been possible.

by Simone Harland

FAU I-Med Profile Center Immunomedicine

A malfunctioning immune system can cause allergies, autoimmune diseases, chronic inflammation or malignant tumors. The FAU Profile Center Immunomedicine conducts research into the functions and malfunctions of the immune system in a network of various disciplines at FAU, Universitätsklinikum Erlangen, the Max Planck Center for Physics and Medicine and the Max Planck Institute for the Science of Light. The aim is to gain a better understanding of the immunological processes and to find new treatment approaches for immune mediated diseases.

This article is part of the FAU Magazin

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