Immunotherapy through TCR gene transfer
Immunotherapy through TCR gene transfer
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DOI：
10.1038/ni1001-957
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发表时间：
2001-10-01
影响因子：
30.5
通讯作者：
Schumacher, TNM
中科院分区：
文献类型：
--
作者：
Kessels, HWHG;Wolkers, MC;Schumacher, TNM
T淋巴细胞的抗原特异性仅由T细胞受体（TC R） a链和P链决定。因此，TCR链的遗传转移可能是一种有吸引力的策略，可以将理想的病毒或肿瘤抗原特异性强加于细胞毒性或辅助T细胞群体。我们在此描述了在小鼠模型系统中将病毒特异性TCR引入外周T细胞的遗传过程。这些实验表明，通过TCR基因转移重定向的T细胞在病毒感染小鼠后扩增并有效地归巢到效应位点。在这种情况下，TCR基因转移与任何显著的自身免疫病理无关。此外，少量tcr转导的T细胞促进了体内表达抗原的肿瘤的排斥反应。这些数据表明，通过TCR基因转移重定向T细胞是一种快速诱导病毒或肿瘤特异性免疫的可行策略。
The antigen specificity of T lymphocytes is dictated solely by the T cell receptor (TC R) a and P chains. Consequently, genetic transfer of TCR chains may be an appealing strategy with which to impose a desirable virus- or tumor-antigen specificity onto cytotoxic or helper T cell populations. We describe here the genetic introduction of a virus-specific TCR into peripheral T cells in a mouse model system. These experiments showed that T cells redirected by TCR gene transfer expanded upon viral infection of mice and efficiently homed to effector sites. In this setting,TCR gene transfer was not associated with any significant autoimmune pathology. In addition, small numbers of TCR-transduced T cells promoted the rejection of antigen-expressing tumors in vivo. These data suggest that the redirection of T cells by TCR gene transfer is a viable strategy for the rapid induction of virus- or tumor-specific immunity.