In the future, the use of genetically modified immune cells may not be limited to tumors, as preliminary results indicate the possibility of employing them in the treatment of difficult-to-control autoimmune diseases.
Rheumatoid arthritis is a chronic disease in which the immune system mistakenly attacks the body's own tissues, particularly the joints. This causes inflammation, swelling, and recurring pain, and over time can lead to joint damage and reduced mobility.
Current treatments help control inflammation and slow disease progression, but they do not cure the disease. Therefore, many patients require long-term treatment, and medication may be necessary for life.
Researchers believe that part of the problem may lie in a type of immune cell known as B cells. Some of these cells transform into memory cells that can remain in various parts of the body, such as lymph nodes, bone marrow, and joint tissues, and continue to produce antibodies that attack the body's own tissues.
Based on this, the researchers tested the possibility of using CAR-T cells to target and eliminate these B cells.
This type of treatment has been used for years to treat certain types of cancer. The process begins by extracting T cells from the patient's blood, then genetically modifying them in the laboratory to equip them with a synthetic receptor called the chimeric antigen receptor (CAR). This receptor acts as a tool that enables the T cells to recognize and attack specific cells.
In the rheumatoid arthritis experiment, researchers engineered CAR-T cells to recognize a molecule called CD19, which is found on the surface of most B cells. The modified cells could then seek out and destroy cells carrying this molecule.
Before CAR-T cells are reintroduced into the patient's body, the patient undergoes a short preparatory chemotherapy treatment that temporarily reduces the number of certain immune cells, giving the modified cells a greater opportunity to multiply and function efficiently. After being administered, the CAR-T cells begin targeting CD19-expressing B cells.
The goal is not just to reduce the number of B cells for a short period, but researchers hope that eliminating disease-causing B cells will reshape immune memory, so that the immune system returns to working closer to its normal state.
In the first phase of the "COMPARE" trial, the first clinical trial of its kind to evaluate CAR-T therapy targeting CD19 in patients with rheumatoid arthritis, six patients received treatment at Charité – University Hospital of Berlin.
The participants, three women and three men aged between 31 and 69, had severe cases of the disease and had not responded adequately to previous treatments.
The main question facing the researchers was whether CAR-T cells were able to reach the disease-causing B cells, including those in deep tissues, and whether the treatment was both safe and effective.
The results showed a clear decrease in disease activity in the six patients. During a year of follow-up, three of them achieved a state of sustained remission (i.e., the disease significantly declined and entered a dormant phase) without the need for medications to treat rheumatoid arthritis.
The results did not stop at improving the symptoms of the disease. The researchers found that the treatment targeted the disease-causing B cells in different parts of the body, including the bone marrow, lymph nodes, and joint tissues.
Levels of autoantibodies associated with rheumatoid arthritis also decreased significantly during the follow-up period.
In contrast, the B cells that attack the body's own tissues are no longer detectable in most patients, which supports the researchers' hypothesis that the treatment may be able to reset the immune memory associated with the disease, rather than just temporarily suppressing inflammation.
Another striking finding was that protective antibodies produced by previous vaccinations, such as those against chickenpox and tetanus, remained largely intact. This suggests that the treatment, despite its profound effect on B cells, may preserve an important part of the immune system's protective memory.
Despite the encouraging results, researchers emphasize that CAR-T therapy for rheumatoid arthritis is still in the experimental stage, the number of patients in the study is small, and the follow-up period is still relatively short to judge the long-term effectiveness of the treatment.
Not all patients responded in the same way; some did not achieve complete remission, and the disease reappeared in one participant after an initial period of remission.
The researchers plan to expand the second phase of the trial to include ten additional patients, comparing CAR-T cell therapy with an approved rheumatoid arthritis drug that also targets B cells.
This phase will help determine whether the modified cell therapy provides a stronger and more lasting effect than current treatments, and whether it is actually able to reset the immune memory that underlies the disease.
