Chimeric Fv-ξ or Fv-ε receptors are not sufficient to induce activation or cytokine production in peripheral T cells
Chimeric Fv-ξ or Fv-ε receptors are not sufficient to induce activation or cytokine production in peripheral T cells
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DOI：
10.1182/blood.v96.5.1999.h8001999_1999_2001
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发表时间：
2000-09-01
期刊：
影响因子：
20.3
通讯作者：
Brocker, T
中科院分区：
文献类型：
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作者：
Brocker, T
在目前的临床试验中，融合到来自TCR-Zeta或Fc(Epsilon)RI伽马链的信号域的嵌合抗体样受体被测试其体内溶解肿瘤细胞的能力。在这项研究中，我们研究了表达这种受体的原代T细胞在转基因小鼠中的功能。这些受体不能诱导静息T细胞的增殖，也不能触发产生最适量的细胞因子。进一步证明，最初低水平存在的细胞因子信息和蛋白正在相当快地消失，而在同一细胞中，内源性TCR/CD3的触发导致正常长时间的细胞因子产生。在外源性白介素2存在的情况下，表达嵌合受体的T细胞体内肿瘤排斥反应增加，进一步强调了这些发现的直接临床相关性。因此，使用转导单链受体的原代T细胞进行过继T细胞治疗可能会从伴随细胞因子的应用中获益良多，(C)2000，由美国血液学学会发表。
In current clinical trials, chimeric antibody-like receptors fused to signaling domains derived from TCR-zeta or Fc(epsilon)RI gamma-chain are tested for their ability to lyse tumor cells in vivo. In this study, the function of primary T cells expressing such receptors has been investigated in transgenic mice. These receptors cannot induce proliferation of resting T cells or trigger the production of optimal amounts of cytokines. It is further demonstrated that an initial low presence of cytokine message and protein is disappearing rather fast, whereas the triggering of endogenous TCR/CD3 in the same cells leads to normal prolonged cytokine production. The direct clinical relevance of these findings is further underlined by the increased in vivo tumor rejection by T cells expressing chimeric receptors in presence of exogenous interleukin-2. Therefore, adoptive T-cell therapy using primary T cells transfected with single chain receptors might benefit substantially from the accompanying administration of cytokines,(C) 2000 by The American Society of Hematology.