What do type 1 diabetes, Crohn’s disease and lupus have in common? They’re all autoimmune diseases. Such conditions affect hundreds of millions of people worldwide, yet current treatments manage symptoms rather than curing disease. We spoke to Professor Yannick Muller, Assistant Professor at the University of Lausanne (UNIL) and Senior Consultant at the Lausanne University Hospital (CHUV), about the possible uses for CAR T-cell therapy in treating autoimmune diseases.

The selectivity problem

Autoimmune diseases occur when the body attacks regular cells, believing them to be foreign. As Yannick put it, ‘An immune response is all about recognising the difference between “self” and “non-self”. Sometimes our body gets it wrong and it attacks itself.’ There are over 80 recognised autoimmune diseases, and instances are on the rise, with as many as one in ten people being affected.

There are three main factors affecting likelihood: genetic predisposition, a history of infections and gender (women are more susceptible because of certain autoreactive proteins associated with X chromosomes). Many current treatments, however, only manage the condition rather than addressing the root cause. While some autoimmune diseases, such as type 1 diabetes, are primarily managed by replacing the function of cells already destroyed by the immune system, others, such as lupus, are managed largely through systemic immunosuppression, which often carries significant side effects. In both cases, current treatments largely fail to address the underlying immune dysfunction.

‘One of the major problems with the drugs used to treat autoimmune diseases is that they’re not selective,’ Yannick explained. ‘You want to deplete the pathogenic B cells, but you also deplete other cells in the process, including the “good” B cells that make antibodies against infectious diseases. The holy grail in treating autoimmune diseases would be the ability to selectively treat the sick cells. But we’re not there yet.’

The buzz around immune resetting

As of today, only one approach has proved effective in curing someone from an autoimmune disease: bone marrow transplantation. This procedure completely ‘resets’ the immune system. However, with a 5–10% chance of death, the odds are understandably unacceptable for most autoimmune patients. That’s why the hunt is on for more precise immune-resetting techniques, with the potential to treat severe refractory cases.

CAR T-cell therapy could be one of them: a personalised treatment that genetically alters a patient’s own white blood cells. Yannick explained why it has so much potential: ‘A cell is a living drug – conceptually very different from something that acts by passive diffusion.’ But for many years, nobody was interested in using patients’ own cells to treat diseases. It was only in 2012, when CAR T-cell therapy cured a case of acute lymphoblastic leukaemia in a six-year-old, that this approach caught the attention of scientists. ‘That case was a turning point,’ Yannick said. ‘It showed the world that your own cells could be the key to successful treatment.’

Could it work for autoimmune diseases?

Yannick highlighted the dangers of taking a copy–paste approach to protocols: ‘We can’t assume it will work the same way for two different diseases.’ He cited the example of the COVID-19 vaccine, which was primarily developed for elderly people but eventually given to young people. ‘It showed some unanticipated cases of cardiotoxicity,’ Yannick pointed out, ‘because the immune system differs greatly between young and old individuals.’ The same risk exists with CAR T-cell therapy; it is not ideal to apply oncology protocols to autoimmune patients without adjustment.

Yet, early trials gave researchers and patients reasons to be enthusiastic. In 2020, a young woman in Germany with severe treatment-refractory lupus achieved complete remission after a single CAR T-cell infusion. Yannick explained: ‘The cells were so efficient that the patient could stop all their other drugs, and the disease didn’t come back – it was an unexpected outcome that highlights the transformative potential of this therapy.’

Conventional immunosuppressive drugs tackle the underlying inflammatory mechanisms causing a symptom. However, they are insufficient to cure the disease, requiring prolonged administrations with risks of relapse. The advantage of CAR T-cell therapy is that it can reset the pathogenic immune repertoire without the need for bone marrow transplantation.

But how does it actually work?

Lupus is a particularly good candidate for CAR T-cell therapy because it is caused by a pathogenic B-cell response. With CAR T-cell therapy, there is a sequence of depletion and regrowth of B cells. Essentially, the CAR T cells specifically target disease-causing B cells while allowing naïve B cells to bring about immune reconstitution. Within a few months, the engineered CAR T cells disappear completely, and the patient has a new pool of non-autoreactive B cells.

Yannick outlined the benefits of this ‘new’ immune system: ‘The new B cells aren’t trained memory cells. It’s like repopulating all your lymph nodes from scratch.’ But he also emphasised the longer-term impact. ‘After treatment, your immunity is so depleted that it takes a year or two, with a full vaccination programme and careful management of your overall health, to regain normal function.’

Moreover, despite CAR T-cell therapy’s versatility, Yannick stressed that predisposition can’t be cured. ‘Being unfortunate enough to develop the disease doesn’t rule out doing so again after treatment,’ he pointed out. Nevertheless, for patients with limited treatment options, the possibilities sound miraculous.

These remarkable results have raised hopes that CAR T-cell therapy could fundamentally change how we treat autoimmune diseases. However, recent safety concerns have highlighted the challenges that remain. In August 2026, Novartis suspended eight clinical trials following three deaths associated with severe inflammatory complications. Yannick clarified: ‘Some patients showed an overproduction of cytokines, immune-signalling proteins that can trigger dangerous inflammation. No one was really expecting this in autoimmune diseases given that the number of target cells is substantially lower than in haematological malignancies. These events underscore the urgent need to better understand the mechanisms driving CAR T-cell toxicities and develop safer treatment strategies.’

Yannick considered whether the ‘copy–paste’ approach could be the problem. ‘Researchers applied an intensive protocol, which is needed for oncology patients, as you have to eliminate all cancer cells,’ he said. ‘But this might not be necessary for autoimmune patients, as the pathogenic cells are very different in nature. Was that a smart move? There are a lot of open questions to answer now.’ Still, he didn’t think patients would be completely put off engaging with trials: ‘When you’re sick, you think very differently. The risks you’re willing to take change completely.’

So, what now?

Despite this major hurdle for CAR T-cell therapy development, Yannick remains dedicated to finding a way for it to succeed. ‘One possibility is using CAR T cells to suppress B cells instead of killing them,’ he mused, pointing to the Nobel Prize-winning discovery of regulatory T cells in 2025 by Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi. ‘If you don’t have these regulatory T cells, you develop autoimmune disease. They maintain self-tolerance. We’re exploring whether we can use them as a living drug.’

Yannick outlined another approach that’s generating interest in the scientific community: ‘Researchers are asking, could we bring the process directly to the patient? Could we somehow “vaccinate” a patient’s circulating T cells so they start expressing CAR and do the job in vivo?’ That way, you avoid the need to manufacture the cells entirely, but Yannick conceded that progress in this area is still at an early stage: ‘We’re not there yet. It’s much easier to genetically modify T cells outside the body for now.’

Why there’s still hope

For patients with severe refractory autoimmune diseases, CAR T-cell therapy might seem like the ultimate lottery ticket. Early results have been remarkable, but the risks are starkly apparent. During this uncertain time, Yannick remains realistic, but optimistic. ‘There’s a lot of hope,’ he said. ‘But we must be more careful – reassess our safety protocols, improve our understanding of the toxicities that come with these therapies and think about how to adapt these approaches so they’re safer for autoimmune patients’.