In a groundbreaking clinical trial, three individuals suffering from severe autoimmune diseases have entered remission following a novel CAR T cell therapy using donor-derived, CRISPR-modified immune cells. This advancement, which marks the first time donor cells have been used to treat autoimmune disorders, could significantly lower costs and expand access to cutting-edge therapies previously limited by the need for personalised treatments.
The trial, led by Dr. Xu Huji at Naval Medical University in Shanghai, demonstrated the potential of this innovative approach by treating systemic sclerosis and autoimmune myopathy in two men and one woman. These patients, who had few remaining treatment options, experienced remarkable improvements in symptoms within weeks of receiving the therapy. One of the patients, Mr. Gong, reported dramatic changes in skin flexibility and mobility just days after treatment. The effects have persisted more than a year later.
This therapeutic breakthrough could be a game-changer for autoimmune diseases, a field in which treatment options have historically focused on suppressing immune activity, often with limited efficacy and significant side effects. CAR T cells, which have revolutionised cancer immunotherapy, target and eliminate B cells responsible for autoantibody production—the hallmark of many autoimmune conditions like lupus, multiple sclerosis, and systemic sclerosis. The added benefit of using donor cells could allow for mass production of CAR T therapies, reducing the time and cost of manufacturing.
Traditionally, CAR T cell therapy involves collecting a patient’s own T cells, genetically modifying them to express chimeric antigen receptors (CARs) that target specific B cells, and then re-infusing them. This process, while effective, is expensive and highly individualised. By contrast, the recent trial used T cells from a healthy 21-year-old donor. These cells were engineered using CRISPR technology to knock out five key genes, preventing them from being rejected by the patient’s immune system while reducing the risk of the graft attacking the host.
The engineered CAR T cells specifically targeted CD19, a receptor found on B cells, effectively depleting both the healthy and pathogenic B cells responsible for the autoimmune attack. Over time, new healthy B cells repopulated the patients’ immune systems without the resurgence of autoimmunity. Six months after treatment, all three patients remained in remission, and two dozen additional patients who received a modified version of this treatment have also shown promising results.
While these early outcomes are highly encouraging, larger trials are necessary to assess long-term safety and efficacy. One key area of concern is the potential emergence of tumors, which has been observed in some cancer patients treated with CAR T cells. Additionally, researchers will need to determine whether the treatment’s effects will endure for years, or if autoimmune symptoms will eventually return.
If successful on a broader scale, donor-derived CAR T cell therapy could represent a paradigm shift in the treatment of autoimmune diseases. With more than 80 conditions tied to immune system dysfunction, this new approach has the potential to bring long-lasting relief to millions of patients worldwide. The scalability of donor-derived CAR T therapies could also make these advanced treatments more accessible to a wider range of patients, marking an important step toward the future of precision medicine.
This trial is a significant stride toward reimagining how we treat complex diseases at the intersection of immune engineering and gene editing, bringing us closer to a world where previously untreatable conditions can be reversed.
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