Methods to manufacture regulatory T cells for cell therapy

Regulatory T cell (T_reg ) therapy has shown promise in early clinical trials for treating graft-versus-host disease, transplant rejection and autoimmune disorders. A challenge has been to isolate sufficiently pure T_regs and expand them to a clinical dose. However, there has been considerable progress in the development and optimization of these methods, resulting in a variety of manufacturing protocols being tested in clinical trials. In this review, we summarize methods that have been used to manufacture T_regs for clinical trials, including the choice of cell source and protocols for cell isolation and expansion. We also discuss alternative culture or genome editing methods for modulating T_reg specificity, function or stability that could be applied to future clinical manufacturing protocols to increase the efficacy of T_reg therapy.