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Engineering the immune system to correct its own flaws

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Researchers have engineered T cells to target and kill a malfunctioning component of the immune system responsible for autoimmune disease, while sparing healthy immune cells that still protect the body. The work brings scientists closer to targeting only the disease-causing cells in autoimmune diseases, which isn't possible now. Some autoimmune diseases occur when a subset of B cells, which respond to specific signatures of pathogens, incorrectly see a person's own tissue as foreign, prompting the rest of the immune system to attack. Currently, strategies to treat autoimmune diseases involve wide-sweeping immunosuppression, which can leave a patient more susceptible to infection; what's more, patients often experience relapse following such treatments. Now, initial results in mice by Christoph Ellebrecht et al. show that a more targeted approach may be viable for treating autoimmune disease. Inspired by a technique that has recently shown success for treating leukemia, the researchers explored how chimeric antigen receptors (CARs) may be used to target rogue B cells. CAR techniques involve harvesting the antibodies that trigger an immune response and fusing them to pathogen-killing T cells. By tweaking this technique, researchers can create an arsenal of T cells that target a specific pathogen – or in the case of autoimmune diseases, the abnormal B cells. Pemphigus vulgaris (PV) is a life-threatening autoimmune disease that results in blistered skin. Here, the team harvested the key protein, Dsg3, that disease-causing B cells recognize, and fused it to signaling proteins that activate T cells. When the researchers infused mice with the engineered T cells, their levels of Dsg3-targeting B cells decreased, as did the occurrence of blisters. Furthermore, these engineered T cells can divide and proliferate, the researchers show, suggesting that CAR techniques to treat PV, and perhaps other autoimmune diseases, could have long-lasting effects.

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