Immunotherapies have long been used to treat allergies, to reduce the rejection of transplanted organs, and to dampen autoimmunity. Now, scientists at the Mayo Clinic report they have developed an immunotherapy strategy that potentially lays the groundwork for treating a spectrum of autoimmune diseases. Their technique combines chimeric antigen receptors (CAR) with mesenchymal stromal cells (MSC), resulting in engineered stem cells known as CAR-MSCs.

Their findings and new technique are detailed in Nature Biomedical Engineering in an article titled, “Mesenchymal stromal cells with chimaeric antigen receptors for enhanced immunosuppression.”

“Allogeneic mesenchymal stromal cells (MSCs) are a safe treatment option for many disorders of the immune system,” the researchers wrote. “However, clinical trials using MSCs have shown inconsistent therapeutic efficacy, mostly owing to MSCs providing insufficient immunosuppression in target tissues. Here we show that antigen-specific immunosuppression can be enhanced by genetically modifying MSCs with chimaeric antigen receptors (CARs), as we show for E-cadherin-targeted CAR-MSCs for the treatment of graft-versus-host disease in mice.”

“The pioneering approach shows potential in targeting inflammatory disease sites more precisely and improving immunosuppression and healing outcomes,” said Saad Kenderian, a principal investigator and hematologist at Mayo Clinic. “We’re planning to study interventions that minimize the need for long-term medications for autoimmune diseases.”

The combination approach centers on mesenchymal stromal cells, which have the unique ability to transform into several specific types of cells such as bone cells, cartilage cells, and fat cells.

For the study, Kenderian and his team developed CAR-MSCs to specifically target a protein linked to a condition called graft-versus-host disease, as well as inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease.

In mouse models, upon stimulation by the specific protein they were designed to target, CAR-MSCs showed improved ability to go to the inflamed area, have better control of inflammation, and improve outcomes and survival. This was mediated by a change in the genetic signature of CAR-MSCs, the proteins they released, and receptor expression.

Kenderian emphasizes that these preliminary findings set the stage for future applications of this technology, paving the way to enhance the therapy’s versatility to address various diseases across the autoimmune spectrum.

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