Departments of Microbiology, Immunology and Immunology and Pediatrics, University of California, Los Angeles, 290D Biomedical Sciences Research Building, 615 Charles E. Young Drive South, Los Angeles, CA 90095, USA.
Clin Immunol. 2010 May;135(2):247-54. doi: 10.1016/j.clim.2009.12.003. Epub 2010 Jan 13.
Primary immune deficiencies (PID) are due to blood cell defects and can be treated with transplantation of normal hematopoietic stem cells (HSC) from another person (allogeneic). Gene therapy in which a patient's autologous HSC are genetically corrected represents an alternative treatment for patients with PID, which could avoid the immunologic risks of allogeneic HSCT and confer similar benefits. Recent clinical trials using gene therapy have led to immune restoration in patients with X-linked severe combined immune deficiency (XSCID), adenosine deaminase (ADA)-deficient SCID and chronic granulomatous disease (CGD). However, severe complications arose in several of the patients in whom the integrated retroviral vectors led to leukoproliferative disorders. New approaches using safer integrating vectors or direct correction of the defective gene underlying the PID are being developed and may lead to safer and effective gene therapy for PID.
原发性免疫缺陷病（PID）是由于血细胞缺陷引起的，可以通过移植来自他人的正常造血干细胞（HSC）进行治疗（同种异体）。基因治疗是对患者自身的 HSC 进行基因纠正，代表了 PID 患者的一种替代治疗方法，它可以避免同种异体 HSCT 的免疫风险，并带来类似的益处。最近使用基因治疗的临床试验导致 X 连锁严重联合免疫缺陷（XSCID）、腺苷脱氨酶（ADA）缺陷性 SCID 和慢性肉芽肿病（CGD）患者的免疫恢复。然而，在一些整合逆转录病毒载体导致白细胞增生性疾病的患者中出现了严重并发症。正在开发使用更安全的整合载体或直接纠正 PID 潜在缺陷基因的新方法，这可能会为 PID 带来更安全有效的基因治疗。
