Harnessing the inherent power of chimeric antigen receptor (CAR)-expressing regulatory T cells (CAR-Tregs) to treat autoimmune-related disorders.

Abstract

Over the past years, adoptive cell therapy with regulatory T lymphocytes (Tregs) has captured the attention of many scientists and clinicians as a novel promising approach for treating a wide range of immune-mediated disorders. In particular, the robust immunosuppressive properties of these cells have been demonstrated to make them uniquely valuable for the treatment of autoimmune diseases. More recently, it has been brought to light that adoptive transfer of chimeric antigen receptor (CAR) Tregs (CAR-Tregs) can also serve a protective role against autoimmune-related disorders. Interestingly, a growing body of evidence indicates that the beneficial and therapeutic effects of antigen-specific CAR-Tregs surpass those of polyclonal Tregs in treating autoimmune conditions. Therefore, harnessing and adapting CAR technology to generate more specific and effective CAR-Tregs, both in terms of tissue localization and antigen recognition, may lay the foundations for the development of far more potent immunotherapeutic strategies for autoimmune-related disorders. Herein, we first highlight the major immunosuppressive abilities of CAR-Tregs and further summarize the current findings on their potential applications in treating autoimmune-related disorders. Then, we will attempt to address the practical challenges in the clinical use of CAR-Treg therapies.