Gene transfer into hematopoietic stem cells as treatment for primary immunodeficiency diseases
Gene transfer into hematopoietic stem cells as treatment for primary immunodeficiency diseases
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DOI：
10.1007/s12185-014-1524-z
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发表时间：
2014-04-01
影响因子：
2.1
通讯作者：
Candotti, Fabio
中科院分区：
文献类型：
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作者：
Candotti, Fabio
基因转移到造血干细胞已经显示出治疗多种血液系统疾病的潜力。原发性免疫缺陷疾病已成为这一领域基因治疗的典范和典范。过去15年的临床结果表明，x连锁严重联合免疫缺陷、腺苷脱氨酶缺乏症、慢性肉芽肿病和Wiskott-Aldrich综合征等疾病可以得到显著改善，甚至治愈。不幸的是，随着最初明确的临床益处，基因治疗的第一个严重并发症也发生了。在使用基于小鼠γ -逆转录病毒并携带强大病毒增强因子的载体治疗的大量患者中，插入性肿瘤发生事件导致急性白血病，在某些情况下具有致命的后果。这些严重的不良事件引发了对整合基因转移治疗血液病的风险和益处评估的修订，并促使新一代具有公认的优越安全性的病毒载体的开发和应用。本文综述了基因治疗原发性免疫缺陷的临床经验，并讨论了这一不断扩大的临床研究领域未来发展的可能进展途径。
Gene transfer into the hematopoietic stem cell has shown curative potential for a variety of hematological disorders. Primary immunodeficiency diseases have led to the way in this field of gene therapy as an example and a model. Clinical results from the past 15 years have shown that significant improvement and even cure can be achieved for diseases such as X-linked severe combined immunodeficiency, adenosine deaminase deficiency, chronic granulomatous disease and Wiskott-Aldrich syndrome. Unfortunately, with the initial clear clinical benefits, the first serious complications of gene therapy have also occurred. In a significant number of patients treated using vectors based on murine gamma-retroviruses and carrying powerful viral enhancer elements, insertional oncogenesis events have resulted in acute leukemias that, in some cases, have had fatal outcomes. These serious adverse events have sparked a revision of the assessment of risks and benefits of integrating gene transfer for hematological diseases and prompted the development and application of new generations of viral vectors with recognized superior safety characteristics. This review summarizes the clinical experience of gene therapy for primary immunodeficiencies and discusses the likely avenues of progress in the future development of this expanding field of clinical investigations.