Brocker T
Institute for Biology III, Department of Molecular Immunology at the Max-Planck-Institute for Immunobiology, Basel, Switzerland.
Blood. 2000 Sep 1;96(5):1999-2001.
In current clinical trials, chimeric antibody-like receptors fused to signaling domains derived from TCR-zeta or Fc(epsilon)RIgamma-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. (Blood. 2000;96:1999-2001)
在当前的临床试验中，对与源自TCR-ζ或Fc(ε)RIγ链的信号结构域融合的嵌合抗体样受体在体内裂解肿瘤细胞的能力进行了测试。在本研究中，已在转基因小鼠中研究了表达此类受体的原代T细胞的功能。这些受体不能诱导静息T细胞增殖，也不能触发最佳量细胞因子的产生。进一步证明，细胞因子信息和蛋白质最初的低水平存在会很快消失，而在相同细胞中内源性TCR/CD3的触发会导致正常的细胞因子长期产生。在存在外源性白细胞介素-2的情况下，表达嵌合受体的T细胞在体内的肿瘤排斥反应增加，进一步强调了这些发现的直接临床相关性。因此，使用转染了单链受体的原代T细胞进行过继性T细胞治疗可能会从伴随给予细胞因子中受益匪浅。（《血液》。2000年；96:1999 - 2001）
