Shah Khalid, Tung Ching-Hsuan, Breakefield Xandra O, Weissleder Ralph
Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Mol Ther. 2005 Jun;11(6):926-31. doi: 10.1016/j.ymthe.2005.01.017.
Therapeutic proteins with specific effector functions play an increasingly important role in drug therapy. For example, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) predominantly kills cancer cells, while sparing normal cells. Here, we report the use of a secreted version of TRAIL as a therapeutic protein that induces apoptosis and kills surrounding cells in vivo, thus resulting in the dramatic reduction of glioma burden in mouse tumor models. Using a caspase-3-activatable aminoluciferin, we were able to show the induction of apoptosis specifically in S-TRAIL vector-infected gliomas. We also show that S-TRAIL-mediated apoptosis and resulting changes in tumor burden can be imaged in the same animal by dual-substrate bioluminescence imaging. The use of S-TRAIL as a therapeutic protein and the ability to image noninvasively both apoptosis and any other cellular events in real time have important clinical implications.
具有特定效应功能的治疗性蛋白质在药物治疗中发挥着越来越重要的作用。例如，肿瘤坏死因子相关凋亡诱导配体（TRAIL）主要杀死癌细胞，而对正常细胞无损害。在此，我们报告使用分泌型TRAIL作为一种治疗性蛋白质，其在体内可诱导凋亡并杀死周围细胞，从而使小鼠肿瘤模型中的胶质瘤负荷显著降低。使用可被半胱天冬酶-3激活的氨基荧光素，我们能够证明在感染S-TRAIL载体的胶质瘤中特异性诱导了凋亡。我们还表明，S-TRAIL介导的凋亡以及由此导致的肿瘤负荷变化可通过双底物生物发光成像在同一只动物体内进行成像。将S-TRAIL用作治疗性蛋白质以及实时无创成像凋亡和任何其他细胞事件的能力具有重要的临床意义。
