T-cell mediated rejection of gene-modified HIV-specific cytotoxic T lymphocytes in HIV-infected patients
T-cell mediated rejection of gene-modified HIV-specific cytotoxic T lymphocytes in HIV-infected patients
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DOI：
10.1038/nm0296-216
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发表时间：
1996-02-01
期刊：
影响因子：
82.9
通讯作者：
Greenberg, PD
中科院分区：
文献类型：
--
作者：
Riddell, SR;Elliott, M;Greenberg, PD
在体细胞中导入和表达基因是纠正遗传缺陷疾病和增强免疫功能的一种创新疗法。基因治疗的一个潜在障碍是通过对引入的基因的新蛋白质产物的免疫反应来消除这种基因修饰的细胞。我们正在进行一项免疫治疗试验，在该试验中，人类免疫缺陷病毒(HIV)血清阳性的个人接受经逆转录病毒转导修饰的CD8(+)HIV特异性细胞毒T细胞，以表达允许正选择和负选择的基因。然而，六名受试者中有五人产生了针对新蛋白的细胞毒性T淋巴细胞反应，并消除了转导的细胞毒性T细胞。这些免疫受损的宿主对转基因细胞的排斥表明，为了成功地对具有免疫能力的宿主进行基因治疗，需要采取策略使转基因细胞不太容易受到宿主的免疫监视。
The introduction and expression of genes in somatic cells is an innovative therapy for correcting genetic deficiency diseases and augmenting immune function. A potential obstacle to gene therapy is the elimination of such gene-modified cells by an immune response to novel protein products of the introduced genes. We are conducting an immunotherapy trial in which individuals seropositive for human immunodeficiency virus (HIV) receive CD8(+) HIV-specific cytotoxic T cells modified by retroviral transduction to express a gene permitting positive and negative selection. However, five of six subjects developed cytotoxic T-lymphocyte responses specific for the novel protein and eliminated the transduced cytotoxic T cells. The rejection of genetically modified cells by these immunocompromised hosts suggests that strategies to render gene-modified cells less susceptible to host immune surveillance will be required for successful gene therapy of immunocompetent hosts.