In a recent review published in the journal Clinical Reviews in Allergy & Immunology, researchers explore how CAR T-cell therapy, already used in oncology, could be adapted for use in difficult-to-treat autoimmune diseases such as lupus, in which the immune system attacks healthy tissue.
What is CAR T-cell therapy and how does it work?
CAR T-cell therapy consists of the use of the patient's own T lymphocytes, which are genetically modified in the laboratory to express a chimeric antigen receptor (CAR). This receptor enables the T cells to recognise a specific target on the surface of other cells with high precision.
In oncology, this strategy has transformed the treatment of some blood cancers. In the context of autoimmune diseases, CAR T-cells can be designed to target B cells that contribute to the abnormal functioning of the autoimmune response. These cells, which are altered in many autoimmune diseases, play a central role in the production of autoantibodies that attack the body's own organs and maintain chronic inflammation.
How can CAR T-cell therapy improve the treatment of lupus?
Early studies in humans show that some people with severe, treatment-resistant lupus can achieve sustained remission after receiving this type of immunotherapy. In addition, the safety profile observed so far indicates fewer serious side effects than those reported in some oncological therapies.
Although the available data are still limited and follow-up periods are relatively short, meaning that larger clinical trials are needed, these findings suggest that CAR T-cells cannot only fight blood cancers, but also reprogramme the immune system to treat other complex diseases.
Lupus today: available treatments and their limitations
Systemic lupus erythematosus (SLE) is a chronic and highly heterogeneous autoimmune disease in which a dysregulated immune response leads to the production of autoantibodies, systemic inflammation, and progressive damage to multiple organs.
Current treatment aims to control disease activity and prevent relapses through a combination of treatments, including:
- Antimalarials such as hydroxychloroquine.
- Corticosteroids.
- Conventional immunosuppressants (such as methotrexate, mycophenolate, azathioprine, cyclophosphamide) and biological therapies that mainly target B cells or cytokine pathways, such as belimumab or anifrolumab.
Despite these advances, a significant proportion of patients experience either an insufficient response or cumulative toxicity, highlighting the need for new, more effective and longer-lasting therapeutic strategies.
Beyond lupus: new opportunities for CAR T-cell therapy in other autoimmune diseases
CAR T-cell therapy has shown significant advances in other treatment-resistant autoimmune diseases.
- In systemic sclerosis, reductions in disease activity have been reported, along with stabilisation or improvement in the function of affected organs.
- In idiopathic inflammatory myopathies, patients treated with CAR T-cells have demonstrated an improvement in muscle strength and inflammatory parameters.
- In rheumatoid arthritis, CAR T-cell therapy has been associated with a marked reduction in joint damage in patients whose disease is highly resistant to conventional treatments.
- In primary Sjögren's syndrome, a decrease in systemic symptoms and normalisation of blood markers have been observed.
Overall, CAR T-cell therapy represents a conceptually new approach to treating severe autoimmune diseases. Rather than continuously suppressing the immune system, it may allow for deep immune reprogramming by targeting B cells and the T lymphocytes with which they interact.
Although this strategy is still in its early stages, it opens the door to a potential paradigm shift in the treatment of lupus and other treatment-resistant autoimmune diseases.
INFORMATION DOCUMENTED BY:
Dr Manel Juan, Head of the Immunology Department at Hospital Clínic Barcelona.
Dr Gerard Espinosa, internist in the Autoimmune Diseases Department, Director of Medical Education at Hospital Clínic Barcelona.
