Building a CAR-Treg: Going from the basic to the luxury model

Abstract

Regulatory T cells (Tregs) control immune homeostasis and prevent exacerbated immune responses, and can be used as cell therapy to dampen a variety of autoimmune or autoinflammatory responses. Treg therapy is significantly more effective if the cells are antigen-specific. One way to re-direct the specificity of Tregs is to engineer them to express a Chimeric Antigen Receptor (CAR). Proof-of-concept studies have shown the potential for "basic" models of CAR-Tregs to be used as cellular therapy in autoimmunity, organ transplantation and hematopoietic stem cell transplantation. In parallel, work in the context of cancer has significantly advanced knowledge of how to optimise CAR-T cell structure and function for more precise and potent function. In this review, we summarize the current state of knowledge about important considerations when generating CAR-Tregs. We also extrapolate from emerging findings with CAR-T cells about strategies to further improve CAR-Treg function, creating "luxury" models with refined activity.

Keywords: Autoimmunity; Chimeric Antigen Receptor; Regulatory T cells; Signaling; Tolerance; Transplantation.