Regulatory T cells in the era of cell and gene therapy: biology, clinical translation, and future prospects.

Regulatory T cells (Tregs) play a central role in maintaining immune homeostasis. Therefore, owing to their unique immunomodulatory function, their adoptive transfer has been investigated as a novel therapeutic modality. Recent progress in cell manufacturing has allowed the application of Tregs as cell therapy products, and several are being tested in human clinical trials. Furthermore, several clinical trials are aimed at evaluating Treg modulation methods, including cytokine administration, monoclonal antibodies, Treg depletion, and adoptive Treg transfer. Among these, adoptive Treg transfer is a promising cell and gene therapy modality that is potentially beneficial for both genetic and non-genetic diseases, including autoimmunity. To determine the current trends in research on Treg-based therapies, we performed a database search and found that investigational clinical trials have been performed not only for autoimmunity but also for a wide range of diseases. In this mini review, we introduce early benchmarking Treg trials together with recent advances in research on Treg biology shown in non-genetic diseases and not just limited to autoimmunity.