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In September, Belgian biopharmaceutical company UCB, in collaboration with its American partner Biogen, announced promising results for their investigational treatment, dapirolizumab pegol, for systemic lupus erythematosus (SLE). While these two giants plan the second phase 3 study before the end of the year, British researchers have made a notable breakthrough. As part of preliminary trials, three patients benefited from CAR-T cell therapy to genetically treat one of the most severe forms of lupus: systemic lupus erythematosus (SLE). Depending on the results, the therapy could eliminate the need for medication for life.
Lupus, like type 1 diabetes, is an autoimmune disease — resulting from a failure of the immune system, which attacks healthy tissues. This disease mainly affects women aged 15 to 40 and manifests with a variety of symptoms mainly affecting the skin, kidneys, lungs, nervous system and joints. There are an estimated 5 million people suffering from lupus worldwide, including 30 to 40,000 in France and 70,000 in the United Kingdom. This pathology comes in various forms, including systemic lupus erythematosus and discoid lupus, the most widespread.
Discoid lupus is limited to affecting the skin by causing skin lesions, while SLE is characterized by more severe and diffuse immune attacks, often resulting in disabling symptoms such as chronic fatigue, joint pain and inflammation of the main organs.
The exact causes of this autoimmune disease remain unknown, although some studies suggest genetic factors. To date, no cure exists for lupus, forcing patients to take medications for life to alleviate the symptoms. Standard anti-inflammatories, such as ibuprofen, as well as steroid injections, are frequently used to treat mild symptoms. In more severe cases, doctors resort to immunosuppressants and immunomodulators.
However, the treatment of lupus could drastically change for the better: researchers from University College London Hospitals NHS Foundation Trust (UCLH) and University College London have developed a chimeric antigen (CAR-T) cell therapy receptor-T) which consists of genetic reprogramming of the immune system targeting problematic cells. “
Lupus is a disease that requires lifelong treatment, but this therapy could transform that reality, which is extremely exciting “, Professor Ben Parker, consultant rheumatologist at the Manchester Royal Infirmary, told the Guardian.
CAR-T cell therapy: from cancer to lupus
Until now, in the UK, CAR T cell therapies have been used exclusively for certain forms of cancer. Researchers now believe it could show promise in treating a wide range of diseases, such as lupus and multiple sclerosis.
In August 2021, a study published in the New England Journal of Medicine highlighted the success of this therapy in a 21-year-old woman suffering from severe SLE. This form of lupus involves overactivation of autoreactive B lymphocytes, leading to abnormal production of autoantibodies. CAR-T cell therapy works by specifically targeting the transmembrane protein CD19 found on the surface of B cells, providing the first clinical evidence of the effectiveness of CAR-T cell therapies in autoimmune diseases.
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Recently, researchers from UCLH and UCL explored this therapeutic avenue with a first trial on three patients in the United Kingdom. The first patient, a 32-year-old woman named Katherine, was administered CAR-T in July at the National Institute for Health and Care Research clinical research center in Manchester. The other two, including a 50-year-old woman who has had lupus since she was 20, received their treatment last week.
In Germany, lupus patients already benefited from similar therapy last year and remain in remission. Preliminary results indicate that they have not needed medication since then. As for new patients in the United Kingdom, they will be followed over a period of 15 years to assess the long-term effects of the treatment. Katherine has already seen a significant improvement: a few weeks after the therapy, her joints were no longer swollen.
« It is an exciting moment to be able to offer this treatment to lupus patients in this clinical trial said Dr Eleni Tholouli, Director of the Adult Stem Cell Transplantation Unit at Manchester Royal Infirmary. “ We hope that this will bring positive results and open new treatment options for patients with this disease “, she concluded.
