Enhancing human regulatory T cells in vitro for cell therapy applications

Adoptive cellular therapies are gaining popularity as a means to treat clinical conditions, with potentially fewer risks and greater efficacy than traditional pharmacological strategies. Regulatory T cells (Tregs) are currently undergoing clinical trials in various immune-mediated pathologies, including transplant rejection and autoimmune conditions. In general, cell therapy relies upon ex vivo expansion of the cell product, in order to administer more cells than can be isolated from one person. In vitro manipulation of cell therapy products, prior to administration to patients, offers the opportunity to enhance the efficacy of the final cell therapy product in other ways. For example, cells can be exposed to reagents that enhance their longevity or functional potency after transfer into the patient. Genetic modification strategies can even permit the design of cells with bespoke functionality. Crucially, in vitro manipulation of therapeutic cells in isolation can exert these influences upon the biology of the therapeutic cells, without systemic exposure of the patient to the reagents being used. Quality control assessments can be integrated into the procedure prior to administration, to protect the patient from the risk of adverse events, should the procedure produce undesirable results. With a particular focus on Tregs, this review surveys the diverse strategies that are being employed to enhance the efficacy of cell therapy via in vitro manipulation of cells, and highlights some emerging technologies that may propel this endeavour in the future.