Adoptive immunotherapy of disseminated leukemia with TCR-transduced, CD8+ T cells expressing a known endogenous TCR.
Adoptive immunotherapy of disseminated leukemia with TCR-transduced, CD8+ T cells expressing a known endogenous TCR.
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DOI：
10.1038/mt.2008.300
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发表时间：
2009-04
影响因子：
12.4
通讯作者：
Greenberg, Philip D.
中科院分区：
文献类型：
--
作者：
Dossett, Michelle L.;Teague, Ryan M.;Schmitt, Thomas M.;Tan, Xiaoxia;Cooper, Laurence J. N.;Pinzon, Cristina;Greenberg, Philip D.
连续性T细胞免疫疗法在人类恶性肿瘤的治疗中显示出前景，但是在每个患者中分离对肿瘤抗原具有高亲和力的T细胞的挑战限制了这种方法的应用。将编码识别确定的肿瘤相关抗原的高亲和力TCR的T细胞受体（TCR）基因转移到T细胞中可以潜在地绕过这一障碍。使用广泛播散性白血病的过继性T细胞免疫治疗的良好表征的小鼠模型，我们证明了TCR基因修饰的T细胞可以治愈小鼠的播散性肿瘤。这种过继性治疗的一个目标是建立长期记忆应答以防止复发，但是由于在静止的静息T细胞中引入的TCR的体内表达减少，转移的TCR转导的T细胞的长期功能受到限制。然而，通过将TCR引入具有已知内源特异性的细胞中，通过内源TCR的刺激激活这些T细胞可用于增加引入的TCR的表达，潜在地提供增加宿主中肿瘤反应性T细胞的总数并恢复更有效的抗肿瘤活性的策略。
Adoptive T cell immunotherapy has shown promise in the treatment of human malignancies, but the challenge of isolating T cells with high avidity for tumor antigens in each patient has limited application of this approach. The transfer into T cells of T cell receptor (TCR) genes encoding high affinity TCRs recognizing defined tumor-associated antigens can potentially circumvent this obstacle. Using a well-characterized murine model of adoptive T cell immunotherapy for widely disseminated leukemia, we demonstrate that TCR gene-modified T cells can cure mice of disseminated tumor. One goal of such adoptive therapy is to establish a long-term memory response to prevent recurrence, but long-term function of transferred TCR-transduced T cells is limited due to reduced expression of the introduced TCR in vivo in quiescent resting T cells. However, by introducing the TCR into a cell with a known endogenous specificity, activation of these T cells by stimulation through the endogenous TCR can be used to increase expression of the introduced TCR, potentially providing a strategy to increase the total number of tumor-reactive T cells in the host and restore more potent anti-tumor activity.
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影响因子：
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作者：
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