Woods Niels-Bjarne, Bottero Virginie, Schmidt Manfred, von Kalle Christof, Verma Inder M
Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Nature. 2006 Apr 27;440(7088):1123. doi: 10.1038/4401123a.
The development of T-cell leukaemia following the otherwise successful treatment of three patients with X-linked severe combined immune deficiency (X-SCID) in gene-therapy trials using haematopoietic stem cells has led to a re-evaluation of this approach. Using a mouse model for gene therapy of X-SCID, we find that the corrective therapeutic gene IL2RG itself can act as a contributor to the genesis of T-cell lymphomas, with one-third of animals being affected. Gene-therapy trials for X-SCID, which have been based on the assumption that IL2RG is minimally oncogenic, may therefore pose some risk to patients.
在使用造血干细胞进行的基因治疗试验中，三名患有X连锁重症联合免疫缺陷（X-SCID）的患者在其他方面治疗成功后却发生了T细胞白血病，这导致对该方法进行重新评估。利用X-SCID基因治疗的小鼠模型，我们发现矫正治疗基因IL2RG自身可促成T细胞淋巴瘤的发生，三分之一的动物受到影响。因此，基于IL2RG致癌性极小这一假设开展的X-SCID基因治疗试验可能会给患者带来一些风险。
