Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency.
Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency.
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DOI：
10.1126/scitranslmed.aad8856
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发表时间：
2016-04-20
影响因子：
17.1
通讯作者：
Kardava L
中科院分区：
文献类型：
--
作者：
De Ravin SS;Wu X;Moir S;Anaya-O'Brien S;Kwatemaa N;Littel P;Theobald N;Choi U;Su L;Marquesen M;Hilligoss D;Lee J;Buckner CM;Zarember KA;O'Connor G;McVicar D;Kuhns D;Throm RE;Zhou S;Notarangelo LD;Hanson IC;Cowan MJ;Kang E;Hadigan C;Meagher M;Gray JT;Sorrentino BP;Malech HL;Kardava L
X连锁严重联合免疫缺陷（SCID-X1）是一种严重的T、B和自然杀伤（NK）细胞免疫缺陷，由编码几种白细胞介素受体共同链（γ c）的IL 2 RG突变引起。对SCID-X1婴儿进行γ-逆转录病毒（γ RV）基因治疗，无需预处理，即可恢复T细胞免疫，无需B或NK细胞校正，但类似治疗对年龄较大的SCID-X1儿童无效。我们使用慢病毒基因治疗方法治疗5例婴儿期接受过半相合造血干细胞（HSC）移植但仍持续免疫功能障碍的SCID-X1患者。两名老年患者的随访数据表明，非清髓性白消安预处理后，慢病毒载体γ c转导的自体HSC基因治疗实现了基因标记的T、NK和B细胞的选择性扩增，这与治疗后2至3年免疫体液应答的持续恢复和临床改善相关。在三名年轻患者中也实现了类似的基因标记水平，尽管随访时间只有6至9个月。慢病毒基因治疗与降低强度的条件似乎是安全的，可以恢复体液免疫功能，以thaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethalaplosomethal
X-linked severe combined immunodeficiency (SCID-X1) is a profound deficiency of T, B, and natural killer (NK) cell immunity caused by mutations in IL2RG encoding the common chain (γc) of several interleukin receptors. Gamma-retroviral (γRV) gene therapy of SCID-X1 infants without conditioning restores T cell immunity without B or NK cell correction, but similar treatment fails in older SCID-X1 children. We used a lentiviral gene therapy approach to treat five SCID-X1 patients with persistent immune dysfunction despite haploidentical hematopoietic stem cell (HSC) transplant in infancy. Follow-up data from two older patients demonstrate that lentiviral vector γc transduced autologous HSC gene therapy after nonmyeloablative busulfan conditioning achieves selective expansion of gene-marked T, NK, and B cells, which is associated with sustained restoration of humoral responses to immunization and clinical improvement at 2 to 3 years after treatment. Similar gene marking levels have been achieved in three younger patients, albeit with only 6 to 9 months of follow-up. Lentiviral gene therapy with reduced-intensity conditioning appears safe and can restore humoral immune function to posthaploidentical transplant older patients with SCID-X1.
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DOI：
10.1126/science.1254194
发表时间：
2014-07-11
期刊：
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影响因子：
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作者：
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影响因子：
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