title: Use of gene-modified regulatory T-cells to control autoimmune and alloimmune pathology: is now the right time?
abstract: 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.
authors: Department of Medicine, Barnet and Chase Farm NHS Trust, Barnet, Hertfordshire EN5 3DJ, UK.
authors: Hannah
authors: H
authors: Jethwa
authors: King's College London, King's Health Partners Integrated Cancer Centre, Department of Research Oncology, Guy's Hospital Campus, Great Maze Pond, London SE1 9RT, UK.
authors: Antonella A
authors: AA
authors: Adami
authors: King's College London, King's Health Partners Integrated Cancer Centre, Department of Research Oncology, Guy's Hospital Campus, Great Maze Pond, London SE1 9RT, UK; Department of Immunology, Barnet and Chase Farm NHS Trust, Barnet, Hertfordshire EN5 3DJ, UK; Department of Clinical Immunology and Allergy, King's College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, UK. Electronic address: John.maher@kcl.ac.uk.
authors: John
authors: J
authors: Maher
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D018570:Risk Assessment; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
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