期刊
CLINICAL IMMUNOLOGY
卷 150, 期 1, 页码 51-63出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2013.11.004
关键词
Regulatory T-cell; Chimeric antigen receptor; T-cell receptor; FoxP3; Gene therapy; Immunotherapy
类别
资金
- National Institute for Health Research (NIHR) Biomedical Research Centre
- NIHR Clinical Research Facility based at Guy's and St Thomas' NHS Foundation Trust and King's College London
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. (C) 2013 Elsevier Inc. All rights reserved.
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