Santilli Giorgia, Thornhill Susannah I, Kinnon Christine, Thrasher Adrian J
University College London, Institute of Child Health, Centre for Immunodeficiency, Molecular Immunology Unit, 30 Guilford Street, London, WC1N 1EH, UK.
Expert Opin Biol Ther. 2008 Apr;8(4):397-407. doi: 10.1517/14712598.8.4.397.
Primary immunodeficiencies (PID) are a group of inherited diseases that affect the development or activity of the immune system. In severe cases allogeneic haematopoietic stem cell transplantation has proved to be a successful curative modality but it is limited by toxicity and reduced efficacy in mismatched donor settings.
Gene therapy for PID has been developed as an alternative strategy and has entered the clinical arena. In this review we discuss the outcomes of recent gene therapy trials and some of the problems that remain to be tackled.
Results from clinical trials for X-linked severe combined immunodeficiency (SCID-X1), adenosine deaminase deficient SCID (ADA-SCID), and X-linked chronic granulomatous disease (X-CGD) are discussed. In addition, other conditions are highlighted such as the Wiskott Aldrich Syndrome (WAS) for which gene therapy has shown considerable promise in preclinical studies, and are currently being translated into novel clinical approaches.
RESULTS/CONCLUSION: Whilst these encouraging results demonstrate that gene therapy can be used successfully to treat monogenic PID, the occurrence of vector-related side effects has highlighted the need for accurate assessment of the associated risks and a requirement for improvements in vector design.
原发性免疫缺陷病（PID）是一组影响免疫系统发育或功能的遗传性疾病。在严重病例中，异基因造血干细胞移植已被证明是一种成功的治愈方法，但在供体不匹配的情况下，它受到毒性和疗效降低的限制。
PID的基因治疗已作为一种替代策略得到发展，并已进入临床领域。在本综述中，我们讨论了近期基因治疗试验的结果以及一些有待解决的问题。
讨论了X连锁严重联合免疫缺陷病（SCID-X1）、腺苷脱氨酶缺乏性SCID（ADA-SCID）和X连锁慢性肉芽肿病（X-CGD）的临床试验结果。此外，还强调了其他疾病，如维斯科特-奥尔德里奇综合征（WAS），基因治疗在临床前研究中已显示出相当大的前景，目前正在转化为新的临床方法。
结果/结论：虽然这些令人鼓舞的结果表明基因治疗可以成功用于治疗单基因PID，但载体相关副作用的出现凸显了准确评估相关风险的必要性以及改进载体设计的要求。
