Department of Medicine, Barnet and Chase Farm NHS Trust, Barnet, Hertfordshire EN5 3DJ, UK.
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.
Clin Immunol. 2014 Jan;150(1):51-63. doi: 10.1016/j.clim.2013.11.004. Epub 2013 Nov 16.
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.
采用基因靶向 T 细胞的过继免疫疗法最近开始在选定的肿瘤类型中取得显著的临床效果。此外，长期随访研究表明，与造血干细胞不同，整合病毒载体不会在 T 细胞中引起临床明显的遗传毒性。这种临床经验所带来的乐观情绪为考虑在其他疾病类型中扩展使用这项技术提供了一个平台。一个特别引人关注的领域是利用调节性 T 细胞（Tregs）来下调不需要的免疫反应。越来越多的证据支持这种方法在自身免疫性疾病和同种异体移植排斥的临床前模型中的有效性。尽管如此，关于最佳宿主细胞、转基因货物、工程细胞在体内的表型稳定性以及潜在毒性等问题仍存在疑问。在这里，我们回顾了基因工程 Tregs 可以有效抑制致病性免疫反应的证据，并对这种方法的临床开发前景进行了批判性评估。
