Synthetic receptor-based cell therapies for autoimmune diseases: an update.

Increasing frequency of autoimmune diseases is one of the major problems in modern societies. Despite the introduction of new therapeutic agents for autoimmunity over the past several decades, more progress is needed. Synthetic receptor-based cell therapies are being adopted as an option for treating autoimmune diseases from the field of oncology. Currently evaluated strategies can be summarized into two approaches. The first one is the elimination of autoreactive cells by targeting them, for example, with CAR-T or CAAR-T cells. The second is based on rebalancing the proinflammatory milieu with engineered immunosuppressive cells, for example, CAR-Treg. Both approaches can be supplemented with the use of synthetic systems such as Split-CAR, SynNotch, MESA, GEMS, and SNIPR, or prospective off-the-shelf approaches, for example, in situ use of the in vitro transcribed mRNA, ultimately allowing for enhanced efficacy and safety. The primary goal of our review is to provide some perspective on both strategies in basic, translational, and clinical studies with all their advantages and disadvantages to allow for informed future design of adoptive cell therapies for autoimmune diseases.