Engineered Treg cells: The heir to the throne of immunotherapy

Recently, increased interest in the use of Tregs as adoptive cell therapy for the treatment of autoimmune diseases and transplant rejection had led to several advances in the field. However, Treg cell therapies, while constantly advancing, indiscriminately suppress the immune system without the permanent stabilization of certain diseases. Genetically modified Tregs hold great promise towards solving these problems, but, challenges in identifying the most potent Treg subtype, accompanied by the ambiguity involved in identifying the optimal Treg source, along with its expansion and engineering in a clinical-grade setting remain paramount. This review highlights the recent advances in methodologies for the development of genetically engineered Treg cell-based treatments for autoimmune, inflammatory diseases, and organ rejection. Additionally, it provides a systematized guide to all the recent progress in the field and informs the readers of the feasibility and safety of engineered adoptive Treg cell therapy, with the aim to provide a framework for researchers involved in the development of engineered Tregs. •Genetic engineering can produce “disease-custom” Treg therapeutics for the treatment of autoimmune, inflammatory diseases and organ rejection.•A general blueprint of the different approaches, including methods to engineer “off-the-shelf” Treg drugs is provided.•Pros and cons of engineered Treg cells as a therapy and future perspectives are described.