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Current treatments for autoimmune disorders face challenges due to limited knowledge about the specific immune cells involved in each condition. Typically, the initial approach involves immune suppressants, such as steroids or medications used for transplant patients, which broadly inhibit immune activity. This leaves individuals more vulnerable to infections and certain cancers.
Groundbreaking research from the Perelman School of Medicine at the University of Pennsylvania (UPenn) has identified a method to selectively target antibody-producing cells in pemphigus vulgaris (PV), a rare autoimmune disorder, without compromising overall immune health. The findings, recently published in Science, could lead to advancements in treating other autoimmune diseases.
According to Aimee S. Payne, an associate professor of dermatology at UPenn and study author, autoimmune research remains in a primitive state, akin to cancer therapy decades ago when treatments indiscriminately targeted all dividing cells due to a lack of specificity. She shared this insight with mental_floss.
In pemphigus vulgaris (PV), a condition characterized by blistering and sores in mucous membranes, B cells mistakenly target desmoglein-3 (Dsg3), a protein essential for skin cell adhesion. Before the introduction of steroids and Rituximab, the disease was often fatal. Payne notes, 'While patients are no longer dying from PV, they still face significant complications from the treatments.'
Payne and her co-senior author, Michael Milone, adapted their autoimmune approach from chimeric antigen receptor (CAR) therapy, a cancer treatment where T cells are modified to attack cancerous cells in certain leukemias and lymphomas. Although effective, CAR therapy has some side effects. Their version, called CAART (chimeric autoantibody receptor therapy), uses an engineered receptor in mice to selectively target and eliminate only the B cells producing harmful anti-Dsg3 antibodies, leaving other cells unharmed. This approach successfully eradicated Dsg3-targeting cells without causing blistering or autoimmune symptoms in the animals.
Payne explains, 'The strength of CAR technology lies in its precision and effectiveness in eliminating only the targeted cells.'
While CAR T cell therapy in cancer can trigger Cytokine Release Syndrome, a severe inflammatory response, Payne believes CAART is unlikely to cause this issue. 'We’re targeting a very specific subset of B cells, not all of them. In patients with active disease, we’d only eliminate about one percent of total B cells—the ones responsible for the condition.'
Payne states that their research has demonstrated the 'proof of concept' as effectively as cancer CAR therapy did before human trials. The team plans to test the treatment on dogs with PV before advancing to human clinical trials.
Payne explains that the insights gained from applying this novel autoimmune therapy to PV will serve as a 'model for other auto-antibody-driven diseases.' She is optimistic about the future of autoimmune treatment, viewing this advancement as a step toward 'personalized medicine.' This approach involves using genotyping to create tailored therapies for individual conditions, moving away from a generic, one-size-fits-all strategy.
