CAR T-Cell Therapy Puts Severe Rheumatoid

A cancer-fighting cell therapy has put severe rheumatoid arthritis into remission in a small clinical trial. Researchers at Charité - Universitätsmedizin Berlin reported that disease activity fell substantially in all six participants, with three achieving medication-free remission for up to a year.

Immunotherapies like CAR T-cell therapy were first developed to fight cancer. Scientists are now investigating if these personalized treatments, made from a patient's own immune cells, could help treat autoimmune diseases.

Using Cancer Immunotherapy To Reset the Immune System

CAR T cells are engineered to seek out and destroy specific cells. For this rheumatoid arthritis trial, scientists modified patients' T cells with a receptor designed to bind to CD19, a surface molecule found on many B cells. Prof. David Simon of Charité described CD19 as a kind of 'name tag'. Disease-driving B cells in rheumatoid arthritis carry this tag.

Doctors collected T cells from the patients' blood. These cells were genetically modified in a lab to carry the artificial receptor. Patients received a short course of preparatory chemotherapy before a single infusion of their engineered cells. Once inside the body, the CAR T cells search for and attack CD19-positive B cells. This temporarily removes them, potentially allowing the immune system to reset.

First Trial Shows Promising Early Results

The initial phase of the COMPARE trial enrolled six patients with particularly severe, treatment-refractory rheumatoid arthritis. The group included three women and three men aged 31 to 69. Over the previous decade, they had received as many as eight targeted or biologic therapies without adequate disease control.

Prof. Gerhard Krönke, who leads the joint Clinical Rheumatology research group, reported the results. Disease activity decreased markedly in all six patients. During follow-up of up to one year, three patients were in sustained remission without any rheumatoid arthritis medication. Krönke called this remarkable, given that established treatments had previously failed them.

The treatment appeared to reach hidden disease reservoirs. Researchers found the modified immune cells eliminated disease-promoting B cells in deeper locations like bone marrow, lymph nodes, and joint tissue. Levels of rheumatoid arthritis-associated autoantibodies dropped sharply.

David Simon added an important observation. When the B-cell system recovered, predominantly naïve B cells returned. The B cells directed against the body's own tissues, present before treatment, were no longer detectable in almost all patients. This suggests the treatment may reset the pathological immune memory. Antibodies from earlier vaccinations, like those for chickenpox and tetanus, were still detected, indicating protective memory was largely preserved.

Therapy Remains Experimental

The trial suggests a single CAR T-cell treatment can produce a sustained, medication-free remission in some patients. For carefully selected patients whose disease does not respond to available treatments, researchers hope it may eventually be possible to reset immune memory and stop inflammation rather than continuously suppressing it.

However, CAR T-cell therapy for autoimmune diseases is still experimental. Researchers lack long-term experience. Responses differed among the six participants. Some did not achieve a complete response. One patient's disease returned after an initial period of medication-free remission.

Safety findings so far are encouraging. Dr. Marie Luise Hütter-Krönke, Medical Director of the Hematology Early Clinical Trial Unit at Charité, explained the observed side effects. After receiving the CD19 CAR T cells, all participants experienced a temporary, mild-to-moderate cytokine release syndrome (CRS), which was readily manageable. There were no severe neurological complications or other serious adverse events. Infections were rare.

The trial's second phase will include ten additional patients. Researchers plan to compare CAR T-cell therapy with an already approved rheumatoid arthritis drug that also targets B cells.