Could the Immune System Be “Reset”?
Autoimmune diseases happen when the immune system mistakenly attacks the body’s own tissues. For people with severe cases, controlling that immune activity can require years of medications that suppress the immune system.
A 2024 study explored a very different idea: using CAR T-cell therapy to deeply reduce certain B cells involved in autoimmune disease, with the goal of giving the immune system a chance to rebuild in a healthier way.
How Does CAR T-Cell Therapy Work?
CAR T-cell therapy begins with a patient’s own T cells, a type of immune cell. These cells are collected and modified in a laboratory so they can recognize a specific target.
In this study, the modified cells were designed to target CD19, a protein found on B cells. Because abnormal B-cell activity plays an important role in several autoimmune diseases, researchers wanted to see whether removing these cells could lead to long-lasting improvements.
Who Took Part in the Study?
The study included 15 people with severe autoimmune disease who had not responded well to multiple previous treatments.
The group included:
- 8 people with systemic lupus erythematosus (SLE)
- 3 with idiopathic inflammatory myositis
- 4 with systemic sclerosis
Each participant received a single infusion of CD19 CAR T cells after treatment to prepare the immune system. Participants were followed for a median of 15 months, with some followed for as long as 29 months.
Strong Responses Across Three Autoimmune Diseases
The results were especially encouraging in the lupus group. All eight people with lupus reached remission by six months, and disease activity remained absent throughout the available long-term follow-up.
The three participants with inflammatory myositis also achieved major clinical responses, including improvement in muscle function and normalization of important disease markers.
Participants with systemic sclerosis showed decreases in overall disease activity and skin involvement.
Perhaps one of the most notable findings was that all 15 participants were able to stop glucocorticoids and other immunosuppressive medications by the end of follow-up.
What Happened to the B Cells?
After treatment, CD19-positive B cells disappeared rapidly from the bloodstream.
In most participants, B cells eventually returned after several months. Interestingly, the autoimmune diseases generally remained controlled even after B cells came back.
This led researchers to suggest that CAR T-cell therapy may do more than temporarily suppress the immune system. It may help create a kind of immune reset, allowing new B cells to return without immediately restarting the same autoimmune activity.
What About Safety?
Most treatment-related reactions were manageable.
Researchers reported:
- Mild cytokine release syndrome in most affected participants
- One case of moderate cytokine release syndrome
- One mild neurological side effect
- One case of pneumonia requiring hospitalization
No prolonged severe immune-related complications were highlighted during the reported follow-up. Still, CAR T-cell therapy is an intensive treatment and requires close monitoring, especially because patients receive immune-suppressing preparation before the infusion.
A Different Direction for Autoimmune Treatment
Most autoimmune therapies are designed to control the immune system continuously. CAR T-cell therapy is different because it aims to create a major, one-time change in the immune cells driving the disease.
That makes these results particularly interesting. The participants had severe, treatment-resistant disease, yet many experienced sustained improvement after a single CAR T-cell treatment.
The study was small and did not include a control group, so larger randomized trials are still needed. Even so, the findings offer an intriguing look at how cellular therapy may one day help reshape the immune system rather than simply suppress it.
Source
Müller F, Taubmann J, Bucci L, et al. CD19 CAR T-Cell Therapy in Autoimmune Disease — A Case Series with Follow-up. New England Journal of Medicine. 2024;390:687–700. doi: 10.1056/NEJMoa2308917. Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa2308917
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