Adoptive immunotherapy using genetically targeted T-cells has recently begun to achieve impressive clinical impact in selected tumor types. Furthermore, long-term follow-up studies indicate thus far that integrating viral vectors do not elicit clinically evident genotoxicity in T-cells, unlike hematopoietic stem cells. The optimism engendered by this clinical experience provides a platform for consideration of the extended use of this technology in other disease types. One area of particular interest entails the harnessing of regulatory T-cells (Tregs) in order to down-regulate unwanted immune responses. Increasing evidence supports the efficacy of this approach in pre-clinical models of autoimmune disease and allograft rejection. Nonetheless, questions remain about optimal host cell, transgene cargo, phenotypic stability of engineered cells in vivo and potential for toxicity. Here, we review the evidence that genetically engineered Tregs can effectively dampen pathogenic immune responses and critically evaluate the prospects for clinical development of this approach.
Keywords: CAR; CEA; CNS; Chimeric antigen receptor; FoxP3; GITR; Gene therapy; GvHD; Immunotherapy; LTR; MAGE; MOG; RRE; Regulatory T-cell; Rev response element; T-cell receptor; T1DM; TGF-β; carcinoembryonic antigen; central nervous system; chimeric antigen receptor; glucocorticoid-induced TNFR-related protein; graft versus host disease; long terminal repeat; melanoma-associated antigen; myelin oligodendrocyte glycoprotein; tTreg; thymic regulatory T-cell; transforming growth factor-β; type 1 diabetes.
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