Gene therapy for primary adaptive immune deficiencies
Gene therapy for primary adaptive immune deficiencies
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DOI：
10.1016/j.jaci.2011.04.030
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发表时间：
2011-06-01
影响因子：
14.2
通讯作者：
Cavazzana-Calvo, Marina
中科院分区：
文献类型：
--
作者：
Fischer, Alain;Hacein-Bey-Abina, Salima;Cavazzana-Calvo, Marina
基因治疗已成为治疗两种严重联合免疫缺陷 (SCID) 的一种选择：X 连锁 SCID 和腺苷脱氨酶缺乏症。十多年前启动的临床试验结果证明，潜在的 T 细胞免疫缺陷得到了持续且可重复的纠正。成功的治疗基于通过表达治疗性转基因而赋予 T 细胞前体的选择性优势。然而，“第一代”逆转录病毒载体也在一些X连锁SCID患者中引起白血病，因为该构建体倾向于插入祖细胞中的活性基因（例如原癌基因）并通过长末端重复中的病毒元件反式激活癌基因。这些元素已从现在使用的载体中删除。与慢病毒载体（对于转导干细胞更有效）的使用一起，这些进展应该为在原发性免疫缺陷领域安全有效地扩展基因治疗的适应症提供基础。然而，这种扩展必须通过检查正在进行的临床试验的结果来证明。 （过敏临床免疫杂志 2011 年；127：1356-9。）
Gene therapy has become an option for the treatment of 2 forms of severe combined immunodeficiency (SCID): X-linked SCID and adenosine deaminase deficiency. The results of clinical trials initiated more than 10 years ago testify to sustained and reproducible correction of the underlying T-cell immunodeficiency. Successful treatment is based on the selective advantage conferred on T-cell precursors through their expression of the therapeutic transgene. However, "first-generation" retroviral vectors also caused leukemia in some patients with X-linked SCID because of the constructs' tendency to insert into active genes (eg, proto-oncogenes) in progenitor cells and transactivate an oncogene through a viral element in the long terminal repeat. These elements have been deleted from the vectors now in use. Together with the use of lentiviral vectors (which are more potent for transducing stem cells), these advances should provide a basis for the safe and effective extension of gene therapy's indications in the field of primary immunodeficiencies. Nevertheless, this extension will have to be proved by examining the results of the ongoing clinical trials. (J Allergy Clin Immunol 2011;127:1356-9.)