CAR-T – a new opportunity in rheumatology

Treatment of serious autoimmune diseases has improved significantly in recent decades. However, there are patients who do not achieve lasting recovery, no matter how advanced the treatment is. This has created interest in CAR-T in rheumatology.

In the picture you see an illustration of T cells that are programmed to attack B cells that cause disease. 

– Although many of our most seriously ill patients are doing relatively well, I have never experienced anyone getting permanently better after a single treatment, says professor and rheumatologist Øyvind Molberg at Oslo University Hospital – one of the partners in REMEDY.

– CAR-T represents something completely new, and potentially revolutionary, for both researchers and clinicians. Professor Øyvind Molberg

CAR-T therapy was developed for blood cancer, but in recent years has also shown promising results in certain autoimmune diseases. A possible Norwegian initiative in the field is now being prepared.

A researcher crosses his tracks

For Molberg, the work on CAR-T is not a break with previous research, but rather a continuation.

– I worked with human cellular immunology from 1995 to 2008, before many years of clinical rheumatology research. With CAR-T, I have in many ways returned to immunology, he says.

The most important driving force is, however, clinical: the desire to be able to offer more to patients with life-threatening illnesses that cannot be controlled with current treatment.

Convincing study

A clear turning point came in 2022. A study published in Nature Medicine showed that five patients with severe and life-threatening lupus experienced significant improvement after a single treatment, in which their own immune cells were used in a new and targeted way.

– That study convinced me that the potential is real, both in terms of safety, efficacy and biological mechanisms, says Molberg.

For the first time, long-term disease remission was documented in patients who had previously had no effect from available treatment.

CAR-T explained

When Molberg explains CAR-T to patients and relatives, he starts with the basics.

He explains how the immune system normally protects us, and how B cells make antibodies against what is perceived as a threat. In some people, the immune system misinterprets the body's own tissue as dangerous, and triggers an immune reaction that leads to disease.

– If the B cells are driving the disease, the solution may be to remove them – more targeted than with current treatment, he explains.

In CAR-T, the patient's own immune cells (T cells) are taken from the body, modified in a laboratory so that they can recognize the B cells, and then put back in to do this job. These cells are referred to as autologous CD19 CAR-T.

Norwegian CAR-T research in the initial phase

At Oslo University Hospital, an industry-funded study is currently underway in lupus patients with kidney inflammation, and one is planned in ANCA vasculitis. A researcher-initiated study with locally produced CAR-T cells is also underway.

– The most important goal is to build an interdisciplinary, academic environment with both clinical and research expertise in advanced cell therapy for autoimmune diseases.

The ambition is to complement, not compete with, industrial studies – including by illuminating research questions that are difficult to investigate in large commercial studies.

Who can benefit from the treatment?

So far, younger patients with severe, treatment-resistant lupus appear to benefit most from CD19 CAR-T therapy. Promising effects have also been seen in selected patients with severe systemic sclerosis, myositis, and probably rheumatoid arthritis.

Molberg, like many other rheumatologists, believes that CAR-T can eventually be used earlier in the course of the disease in patients with a poor prognosis.

Optimism with reservations

At the same time, he emphasizes the need for sobriety.

“The group of patients who have received CAR-T so far is small. We know little about long-term side effects, and we also don't know whether simpler forms of B-cell treatment can provide a similar effect,” he says.

Before larger efficacy studies can be conducted in Norway, it must first be shown that the treatment can be carried out in a safe and responsible manner – from the production of the cells to the entire treatment process.

A clear signal is missing

Molberg believes that Norway has good conditions for success: strong immunology environments, experience with CAR-T from cancer treatment and a rheumatology professional environment with solid expertise in long-term follow-up.

– What we otherwise lack is a clear signal that national investment in CAR-T and other advanced therapies should not only apply to cancer, but also serious autoimmune diseases.

Looking ahead

Looking 10–15 years ahead, Molberg hopes that increased knowledge about the role of B cells in autoimmune diseases will provide more precise and tailored treatment.

– CAR-T is the most powerful tool we have today, but it is not certain that it will also be the best in the future.

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Facts

Autologous CD19 CAR-T cells

• Autologous : The cells come from the patient themselves.
• T cells : A type of immune cell that normally helps the body fight disease.
• CAR-T : The T cells are modified in a laboratory so that they have a new “target” they can recognize, here primarily B cells.
• CD19 : The name of a protein found on the surface of B cells.

Autoimmune diseases occur when the immune system mistakenly attacks the body's own tissues, creating inflammation and damage.

Remission: When the disease is under control

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The image below is from the National Strategy Meeting for CAR-T Cell Therapy.

- Deep B-cell depletion with CAR-T cell therapy and bi-specific antibodies (BiTE) is the new big thing in the treatment of rheumatology, and could be a revolution for this patient group. We must learn from the hematologists and get such studies to Norway. 

This was stated by the center director for NorTrial's clinical immunology, Jens Vikse, during the National Strategy Meeting – CAR-T and BiTE Studies in Rheumatology in September 2025.