New Immunotherapy Approach for Autoimmune Diseases

Mayo Clinic scientists have created a new immunotherapy strategy for treating a range of autoimmune diseases.

Detailed in a preclinical study published on 04/01/2024 in Nature Biomedical Engineering, the rubric involves combining chimeric antigen receptors (CAR) with mesenchymal stromal cells (MSC), which result in engineered stem cells called CAR-MSCs.

“The pioneering approach shows potential in targeting inflammatory disease sites more precisely and improving immunosuppression and healing outcomes,” says Saad Kenderian, M.B., Ch.B., 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 combinatorial approach centers on mesenchymal stromal cells, which can be found in various tissues in the body, including bone marrow, fat tissue and umbilical cord blood. Uniquely, these cells have the capability to change into bone cells, cartilage cells and fat cells.

Mesenchymal stromal cells are thought to quiesce the immune system, tamping down on inflammation and promoting immune tolerance to prevent the body’s own tissues from attack.

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

The full abstract from the journal article follows–

Allogeneic mesenchymal stromal cells (MSCs) are a safe treatment option for many disorders of the immune system. 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. CAR-MSCs led to superior T-cell suppression and localization to E-cadherin+ colonic cells, ameliorating the animals’ symptoms and survival rates. On antigen-specific stimulation, CAR-MSCs upregulated the expression of immunosuppressive genes and receptors for T-cell inhibition as well as the production of immunosuppressive cytokines while maintaining their stem cell phenotype and safety profile in the animal models. CAR-MSCs may represent a widely applicable therapeutic technology for enhancing immunosuppression.”