Functional human antigen-specific T cells produced in vitro using retroviral T cell receptor transfer into hematopoietic progenitors
Functional human antigen-specific T cells produced in vitro using retroviral T cell receptor transfer into hematopoietic progenitors
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DOI：
10.4049/jimmunol.179.8.4959
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发表时间：
2007-10-15
影响因子：
4.4
通讯作者：
Legrand, Nicolas
中科院分区：
文献类型：
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作者：
van Lent, Anja U.;Nagasawa, Maho;Legrand, Nicolas
具有已知Ag特异性的人T细胞的体外产生对于针对肿瘤和感染的免疫疗法具有主要临床意义。我们已经将TCR α β基因转移到来自出生后胸腺或脐带血的人造血祖细胞中，随后将这些前体细胞培养在表达Notch人配体δ样1的OP 9基质细胞上。我们在这里报告，完全成熟的，功能性T细胞与控制Ag特异性从这样的文化。使用编码针对黑色素瘤（MART-1），病毒（CMV）和次要组织相容性（HA-2）Ag的TCR α β链的载体，我们表明，获得的Ag特异性T细胞对它们的同源Ag发挥细胞溶解活性，并在特异性TCR刺激后在体外扩增。这些结果可能会产生治疗应用，因为它们提供了一种在体外从未分化的造血祖细胞产生大量自体成熟抗原特异性T细胞的方法。
In vitro production of human T cells with known Ag specificity is of major clinical interest for immunotherapy against tumors and infections. We have performed TCR alpha beta gene transfer into human hemopoietic progenitors from postnatal thymus or umbilical cord blood, and subsequently cultured these precursors on OP9 stromal cells expressing the Notch human ligand Delta-like1. We report here that fully mature, functional T cells with controlled Ag specificity are obtained from such cultures. Using vectors encoding TCR alpha beta-chains directed against melanoma (MART-1), viral (CMV), and minor histocompatibility (HA-2) Ags, we show that the obtained Ag-specific T cells exert cytolytic activity against their cognate Ag and expand in vitro upon specific TCR stimulation. Therapeutic applications may arise from these results because they provide a way to produce large numbers of autologous mature Ag-specific T cells in vitro from undifferentiated hemopoietic progenitors.