Extensive freedom from symptoms: Cancer therapy helps with autoimmune diseases

Doctors are treating five people with systemic lupus erythematosus with a therapy that is actually used for cancer.

Extensive freedom from symptoms: Cancer therapy helps with autoimmune diseases

Doctors are treating five people with systemic lupus erythematosus with a therapy that is actually used for cancer. Immunotherapy works for everyone and almost completely eliminates the symptoms. Some experts are already talking about a medical breakthrough.

The success so far has even astonished experts: In the case of a serious autoimmune disease that is considered incurable, a therapy originally developed against cancer has so far resulted in largely freedom from symptoms. So far, the procedure has only been tested on a handful of people at the Erlangen University Hospital, but independent experts are impressed: "The data are so clear that I expect them to be reproduced in larger studies," says immunologist Falk Hiepe von der Berliner charity. The doctors from Erlangen now want to examine the treatment for other serious autoimmune diseases.

In the journal "Nature Medicine", the team led by the immunologist Georg Schett describes the use of the so-called CAR-T cell therapy in people with severe forms of the disease lupus erythematosus. Those treated have been largely symptom-free since the therapy, says Schett, up to now for 5 to 20 months. The group did not observe any serious side effects, which can certainly occur with this method of cancer therapy.

So far it is unclear whether the success of the five patients treated will last and whether it can be transferred to other patients. But an independent expert speaks of a breakthrough: "It's surprising that we're seeing such sweeping success," says rheumatologist Martin Aringer from the Dresden University Hospital. "That advances the field of research." He believes that the approach could possibly also help against some other autoimmune diseases such as multiple sclerosis.

CAR-T cell therapy has only been used in cancer medicine for a few years, but has already established itself against certain leukemias and lymphomas. It works like this: Blood is taken from a patient. Some of the white blood cells, the T cells of the immune system, are then genetically modified in the laboratory in such a way that they carry a specific receptor on their surface: a so-called chimeric antigen receptor (CAR). The patients then get these CAR-T cells back via transfusion.

They should then use the receptor to specifically detect and eliminate cancer cells in the body. However, there is a serious disadvantage: During the course of treatment, neurological complications can occur, but also extremely violent inflammatory reactions, so-called cytokine storms. They are a drastic overreaction of the immune system.

Schett's team is now reporting on the first use of CAR-T cell therapy in people outside of cancer medicine. This is systemic lupus erythematosus (SLE). This rheumatic disease, which progresses in phases, mainly affects women, is usually diagnosed between the ages of 15 and 30 and has not yet been cured.

The severity of the chronic inflammatory disease can vary greatly and range from mild to life-threatening forms. Antibodies formed by B cells of the immune system can cause a wide range of symptoms: from the characteristic redness on the cheeks - the so-called butterfly erythema - to leaden tiredness and joint problems to damage to the nervous system and internal organs such as the heart, lungs and kidneys .

The previous therapies depend on the individual course and include - depending on the severity of the disease - a variety of different drugs: such as antimalarials, anti-inflammatory drugs, immunosuppressants or various antibodies.

The four women and one man aged 18 to 24 who were now being treated in an individual healing attempt had life-threatening forms of the disease, which affected the kidneys, heart, lungs and joints. Because no further treatment worked for them, they were considered for the treatment attempt with immunotherapy.

Your blood T-cells were modified in the laboratory in such a way that they recognize the CD19 receptor, which B-cells specifically carry on their surface, and eliminate these cells: In SLE, the B-cells are primarily responsible for the formation of those antibodies that are causing the problems.

The participants were then given 1 million of these CAR-T cells per kilogram of body weight. By day 9 after the infusion, these had spread so far in the body that they represented 11 to 59 percent of all circulating T cells. After that, the proportion fell again, but the improvement continued.

From the third month, those treated experienced a significant improvement, and this remission has lasted for 5 to 20 months to date, says study director Schett. Particularly important: The participants remained free of symptoms even after the B cells reappeared after an average of 100 days. This suggests that these newly formed B cells are "harmless" and no longer cause autoimmune reactions, says Schett. "We are very confident that this will actually work."

In general, the patients tolerated the treatment well, the team writes, three of the five people had a fever for two to three days. Apparently, treatment for lupus is much better tolerated than for cancer.

"These data indicate that the transfer of CD19 CAR T cells is feasible, tolerable and highly effective," write the physicians. In view of the small number of participants, however, it is unclear whether certain patients are particularly suitable for the therapy and others not.

It is not yet possible to say for sure whether the underlying immune disorder of the patients has been resolved - i.e. whether one can speak of healing. But there are indications of this. "The long disease-free state observed in the first two patients despite return of B cells, the persistent lack of need for immunosuppression, the absence of any SLE flare-ups, and the replenishment of harmless B cells support the idea that after a CAR-T cell therapy can result in a restart of the immune system."

The Dresden expert Aringer assumes that the success of the therapy will last. "20 months is a very long time for this disease," says the internist and rheumatologist, who is a member of the board of the lupus erythematosus self-help community. "The data are impressive and there is no doubt that patients have benefited from them."

In view of the complex procedure and the associated costs, Aringer does not assume that the procedure will become routine therapy. "But in the case of seriously ill people, you will think about it in the future."

The immunologist Thomas Dörner from the Berlin Charité is "very enthusiastic about these results", but points out that the five treated were still very young. "In older SLE patients who have suffered from chronic inflammation for many years due to the disease and who have frequently received cortisone treatments, the irreversible consequences of the inflammation cannot be suppressed in this way."

Schett's team wants to examine the treatment in a larger study from the beginning of next year: According to Schett, not only people with lupus erythematosus can take part in it, but also those with two other serious autoimmune diseases: the muscle disease myositis and systemic sclerosis, also known as scleroderma .

In principle, according to Schett, CAR-T cell therapy could be used for all autoimmune diseases in which B cells play a crucial role. These also included multiple sclerosis, rheumatoid arthritis or blistering skin diseases.

It is unclear whether and when the procedure for SLE will be launched. Approval studies, Schett stressed, would have to be carried out by pharmaceutical companies that could raise the necessary funds to finance them. It is also unclear what price they are likely to charge for the therapy if it is launched on the market. In cancer medicine, the once-administered CAR-T cell therapy is very expensive: It costs around 250,000 to 300,000 euros.

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