CAR-T-cell therapy, originally developed for blood cancers, is showing remarkable promise in treating lupus and other autoimmune diseases by effectively resetting the immune system. Early studies have demonstrated complete remission in patients with uncontrolled lupus, leading to a surge of interest and investment in this therapeutic approach.
CAR-T: A 'Deep Reset' for Autoimmune Diseases
Two years ago, a German study published in Nature revealed that five patients with severe lupus achieved complete remission after undergoing CAR-T-cell therapy. This treatment largely eliminated their rogue immune cells, with the first patient remaining symptom-free for almost four years. Anca Askanase, a rheumatologist at Columbia University, noted the initial skepticism surrounding the possibility of a cure for lupus, but these results have sparked a new wave of optimism. Over 40 lupus patients worldwide have now received CAR-T-cell therapy, with most experiencing drug-free remission. While long-term outcomes are still being monitored, the potential for a functional cure is now within reach.
Fabian Müller, a hematologist-oncologist at the University Hospital of Erlangen, explained that CAR-T-cell therapy works by depleting enough B cells to trigger a "deep reset" of the immune system. The engineered CAR-T cells effectively target and destroy B cells, even those hidden in the body's tissues. Although B-cell counts eventually recover, the new B cells no longer attack the body. The first lupus patient treated with CAR-T is approaching five years of remission, a milestone often associated with cancer cures.
Expanding CAR-T to Other Autoimmune Conditions
Beyond lupus, CAR-T therapy is being explored for other autoimmune diseases, including multiple sclerosis, myositis, and myasthenia gravis. The success of CAR-T has inspired the development of simpler and more cost-effective strategies derived from cancer therapy to target and eliminate errant immune cells. While not all approaches may prove successful, the next few years could mark a turning point in the treatment of these challenging diseases.
Challenges and Limitations of CAR-T
Despite its potential, CAR-T therapy faces significant hurdles. The treatment is complex, expensive (approximately $500,000 for cancer), and requires specialized facilities. Each patient's cells must be re-engineered, making it difficult to scale up production. Patients also require chemotherapy to deplete existing T cells before CAR-T infusion, and lupus patients typically need to taper off their existing medications, which can trigger disease flare-ups. These factors limit CAR-T therapy to patients with severe disease who have exhausted other treatment options.
Emerging Alternatives: Bispecific T-Cell Engagers (BiTEs)
To address the limitations of CAR-T, researchers are exploring simpler strategies for B-cell depletion. Bispecific T-cell engagers (BiTEs) are molecules that bind T cells to B cells, facilitating targeted destruction. Müller described BiTEs as "cheap, fast, uncomplicated," although they may not penetrate tissues as effectively as CAR-T cells. In September, The New England Journal of Medicine published case reports demonstrating successful treatment of autoimmune diseases, including lupus, using the BiTE teclistamab. Other similar BiTEs could potentially be repurposed for autoimmune conditions.
The Future of Autoimmune Disease Treatment
While CAR-T therapy may not become universally accessible due to its cost and complexity, it has paved the way for innovative treatment strategies. Simpler therapies like BiTEs may prove "good enough" for many patients and offer a more practical solution for the millions affected by lupus worldwide. Even if CAR-T itself is not widely adopted, it has sparked new ideas that could revolutionize the treatment of autoimmune diseases.
