CAR-T cell therapy has already transformed the treatment landscape for hematologic cancers such as leukemias and lymphomas. Now, a new and promising chapter of this approach is being explored in the field of autoimmune diseases and, more recently, severe allergies. A high-impact study published in the scientific journal Allergy in 2025 presented concrete evidence of the therapeutic potential of CAR-T cells in patients with lupus, systemic sclerosis, and idiopathic inflammatory myopathies.
This article explores how CAR-T therapy is expanding beyond cancer, being applied to the treatment of autoimmune and allergic diseases, and why this approach represents one of the most promising in contemporary precision medicine.
What is CAR-T cell therapy?
CAR-T cells, or chimeric antigen receptor T lymphocytes, are genetically modified to recognize and eliminate specific target cells. Initially developed to attack tumor cells expressing antigens such as CD19, these cells have proven highly effective in hematologic cancers. Now, the same principle is being applied to target autoreactive immune cells involved in autoimmune diseases and severe allergies. CAR-T cells transiently eliminate autoreactive B lymphocytes, allowing the regeneration of a tolerant immune system.
Promising results in autoimmune diseases
The study conducted by Schett and collaborators marked a turning point in the use of cell therapy beyond oncology. Fifteen patients with severe, refractory autoimmune diseases were included: eight with systemic lupus erythematosus (SLE), three with idiopathic inflammatory myopathies (IIM), and four with systemic sclerosis (SSc). All had undergone multiple unsuccessful immunosuppressive treatments.
After infusion of anti-CD19 CAR-T cells, patients experienced rapid cellular expansion in the body, accompanied by near-complete depletion of B cells within a week. This depletion was followed by gradual repopulation around 112 days later, dominated by immature naïve B cells, which reduces the risk of autoimmune recurrence. Even more relevant, all patients showed significant clinical improvement, including discontinuation of immunosuppressants and corticosteroids, as well as normalization of laboratory markers such as anti-DNA antibodies, C3 complement levels, proteinuria, and creatine kinase.
These results reinforce that CAR-T therapy can not only control the disease but also reset the immune system, restoring its balance.
An encouraging safety profile
Safety is a constant concern in any new therapy. In the case of CAR-T for autoimmune diseases, side effects were considered manageable. Most patients experienced only mild, grade 1 cytokine release syndrome (CRS) that did not require intensive care. Only one case of respiratory infection required hospitalization, and another presented a reversible neurological episode (grade 1 ICANS).
Even with massive B-cell elimination, patients maintained an adequate immune response to previously received vaccines, such as those against pneumococcus and SARS-CoV-2. This indicates that while the immune system is reprogrammed, it still retains its capacity for protection against known infections.
What about neurological involvement?
A surprising finding of the study was the therapy’s effectiveness in lupus cases with neurological involvement. CAR-T cells were able to cross the blood–brain barrier and eliminate autoreactive B cells present in the central nervous system. As a result, patients showed rapid and sustained neurological improvement. This represents an unprecedented advance, given the complexity of treating neurological manifestations in autoimmune diseases.
The possibility of use in allergic diseases
Perhaps one of the most intriguing discoveries of the study is the potential extension of CAR-T use to severe allergies. Although still experimental, research in murine and in vitro models has shown that CAR-T cells can be designed to eliminate both pathological IgE-producing B cells and eosinophils, the cells directly involved in exaggerated allergic responses.
Two strategies are being investigated: one focuses on the selective elimination of B cells responsible for producing immunoglobulin E, the main mediator of severe allergic reactions; the other employs chimeric receptors based on interleukin-5 (IL-5), enabling CAR-T cells to identify and eliminate hyperactivated eosinophils. Both approaches still require clinical validation but offer a promising path for diseases such as eosinophilic asthma and severe atopic dermatitis, which currently have limited therapeutic options.
Why CAR-T stands out in autoimmune and allergic diseases
The main advantage of CAR-T therapy is its ability to reprogram the immune system in a lasting way, without the continuous need for immunosuppressive drugs. While conventional therapies act as temporary “brakes” on the immune system, CAR-T cells precisely remove the problem-causing cells, allowing the restoration of healthy immune balance.
Moreover, because CAR-T cells are personalized, they provide a tailor-made treatment adapted to each patient’s immunological profile. This increases efficacy and reduces the risk of severe adverse effects.
Immunoreprogramming and the future of personalized medicine
The immunological understanding behind CAR-T therapy’s efficacy in autoimmune diseases is closely linked to the central role of B cells in the pathogenesis of these conditions. In diseases such as lupus and systemic sclerosis, B cells go beyond antibody production and begin to act as antigen-presenting cells and cytokine-secreting agents, perpetuating the autoimmune response. By selectively eliminating these cells with anti-CD19 CAR-T therapy, treatment acts not only on symptoms but also on the immunopathological root of the disease, promoting a true immune re-education. The regeneration of the B-cell compartment with naïve cells after treatment indicates an “immune reboot,” which may explain the prolonged remissions observed even without continuous immunosuppressive therapy.
This rationale extends to severe allergies, which, although not autoimmune, share the logic of a dysfunctional immune response. Eosinophilic asthma, for example, involves excessive eosinophil activation and IgE production by specific B cells — both potential targets for CAR-T engineering. With advances in biotechnology, it is becoming possible to design increasingly precise chimeric receptors aimed at interacting with unique molecular markers of pathogenic cells, minimizing side effects and optimizing efficacy. This opens a new era of immune-engineered interventions in which each patient’s cells can be programmed to act as highly specific therapeutic agents, shaping the immune system in a controlled and lasting manner.
Challenges to overcome
Despite its enormous potential, CAR-T use outside oncology still faces challenges. The high production cost, the need for specialized infrastructure, and the risk of prolonged immunosuppression are factors that must be carefully assessed. It is also necessary to develop increasingly specific molecular targets, especially for allergies, to ensure that only pathogenic cells are affected.
Even so, the clinical results obtained so far pave the way for broader trials, and companies such as Celluris are investing heavily in the nationalization of these technologies, making them more accessible and sustainable in the long term.
Promising advances
The application of CAR-T therapy in autoimmune and allergic diseases represents one of the most exciting advances in personalized medicine in recent years. Recent studies show that it is possible to achieve long-lasting clinical remission safely and without the need for continuous immunosuppressive treatment. Furthermore, the potential to expand this approach to severe allergic conditions could open a new range of therapeutic options for millions of people currently living with chronic, difficult-to-control diseases.
Read also on our blog: Exploiting nutrient scarcity to increase the potency and safety of CAR-T cells in solid tumors.
