Resetting Autoimmunity with CAR-T Cells

Leon Wirz
Jan 19
4 min read

Nature Medicine, September 2025 | Friedrich-Alexander University Erlangen-Nürnberg (FAU) & German Center for Immunotherapy

Introduction

Autoimmune diseases are conditions in which the immune system attacks the body instead of protecting it. Diseases such as lupus, systemic sclerosis, and inflammatory muscle disorders can affect many organs at once. They often progress slowly, but steadily, over many years. Patients may suffer from pain, fatigue, organ damage, and loss of independence.

Today, most autoimmune diseases cannot be cured. Treatment usually means lifelong medication to calm the immune system. These drugs can reduce symptoms, but they also weaken normal immune defenses and often have side effects. For some patients, even the strongest available therapies are not enough to control the disease.

In cancer medicine, a new approach has changed how doctors think about immune treatment. This approach is called CAR-T cell therapy. Scientists are now asking whether this powerful technology could also be used to rebuild a broken immune system in autoimmune disease, and not just suppress it.

A clinical study called CASTLE suggests that this may be possible.

The Core Discovery

In the CASTLE study, researchers treated patients with a single infusion of modified immune cells called CAR-T cells. These cells were designed to remove B cells, a type of immune cell that plays a key role in many autoimmune diseases.

After treatment, most patients improved quickly. Even more striking, many of them were able to stop all immune-suppressing medication and remained stable for months. This is very unusual in severe autoimmune disease.

The results suggest that the therapy did not simply calm the immune system for a short time. Instead, it may have changed how the immune system works at a deeper level.

How the Study Was Conducted

The CASTLE study was an early clinical trial designed to answer two main questions:Is the treatment safe? And does it show signs that it works?

The study included 24 patients with very severe disease. Ten had lupus, nine had systemic sclerosis, and five had inflammatory muscle disease. All had tried several treatments before, without success.

Doctors first collected the patients’ own T cells from the blood. These cells were then modified in the laboratory so they could recognize and destroy B cells. After a short course of chemotherapy to prepare the body, the modified cells were given back to the patient in a single infusion.

Patients were monitored closely for side effects and improvement over the following months.

Key Findings

Most patients improved clearly after treatment. In lupus, patients reached established remission criteria and disease-related antibodies disappeared from the blood. In systemic sclerosis, lung function stopped worsening and skin thickening improved. Patients with muscle disease regained strength and showed less inflammation.

On the immune level, the treatment removed almost all B cells from the blood. Over time, new B cells appeared again, but they were mostly “new” cells rather than the harmful memory cells linked to autoimmunity. This supports the idea that the immune system was restarted in a healthier way.

Importantly, most patients were able to stop steroids and other immune-suppressing drugs completely.

Limitations of the Study

This study was small and did not include a comparison group. That is normal for early trials, but it means the results must be interpreted with caution. Patients were followed closely for six months, with longer observation still ongoing.

In addition, only patients with very severe disease were included. The results may not apply to people with milder forms of autoimmune disease.

Relevance for Switzerland (including costs)

Autoimmune diseases are expensive for the Swiss healthcare system because they require long-term treatment. Patients with severe disease often need biologic drugs, frequent doctor visits, hospital stays, and long-term monitoring. These costs typically range from CHF 20,000 to CHF 60,000 per year per patient.

Over decades, this can add up to CHF 500,000 or more, not including lost work ability or disability support.

CAR-T therapy is very different. It is expensive upfront (likely CHF 300,000 to CHF 500,000 per patient) but it is given only once. If it leads to long-lasting remission, as seen in this study, it could reduce or even eliminate years of ongoing treatment costs.

For Switzerland, this raises an important question: is it better to pay a large amount once, or smaller amounts every year for decades? In younger patients with severe disease, a one-time therapy could make economic sense over the long term.

Switzerland already has the medical infrastructure needed for such treatments. The main challenge will be deciding who should receive them and how success should be measured.

Potential Impacts of a Successful Therapy

If future studies confirm these results, CAR-T therapy could change the goal of autoimmune treatment. Instead of managing symptoms for life, doctors could aim for long-lasting remission without medication. This would reduce side effects, organ damage, and improve quality of life.

Risks

CAR-T therapy is a powerful treatment and must be used carefully. It temporarily weakens the immune system and can increase infection risk. Treatment requires specialized hospitals and close monitoring. Costs and access will also be limiting factors.

Overall Assessment

The CASTLE study shows that resetting the immune system may be possible in severe autoimmune disease. While the results are early and more research is needed, the findings mark an important step toward a new way of thinking about treatment. Not lifelong suppression, but immune repair.

What Comes Next

Larger studies will be needed to confirm safety and long-term benefits. Researchers will also need to understand which patients benefit most and how durable the effect really is. At the same time, healthcare systems will need to explore how to integrate such therapies responsibly.

Reference

Müller, F., Hagen, M., Wirsching, A. et al. CD19 CAR-T cells for treatment-refractory autoimmune diseases: the phase 1/2 CASTLE basket trial. Nat Med (2026). Link