Engineering precision cell therapy for immune-mediated disease

Autoimmune disease (AID) is a major medical concern for a significant part of the world population. AID comprises a heterogenous group of medical conditions characterized by a shared etiology of the adaptive immune system targeting normal tissue antigens in concert with a breakdown in immune tolerance mechanisms. Until recently, treatment for AID has fallen primarily to systemic therapies including metabolic inhibitors (methotrexate and mycophenolate mofetil), immune suppressants (cyclosporine and corticosteroids), and cytotoxic therapies such as cyclophosphamide for severe manifestations. Although the emergence of novel therapeutics have increased the therapeutic options for patients, the mechanism of action for each of these newer approaches are generally immunosuppressive without specificity towards the aberrant autoimmunity and most are unlikely to restore specific immune tolerance or precisely remove autoreactive cells to permanently cure disease. New approaches to treating AID are still needed, and engineered cell therapy offers a new therapeutic paradigm for addressing pathogenic autoimmunity with the potential to restore immunologic tolerance. Here, we summarize the state of development for precision cell therapy in AID, focusing on redirected T cells to eradicate pathogenic immunity, and antigen specific or engineered regulatory T cells for specific suppression of pathogenic immune responses and restoration of immune tolerance.

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