Cancer: Novel therapeutic strategies that exploit the TNF-related apoptosis-inducing ligand (TRAIL)/TRAIL receptor pathway
Cancer: Novel therapeutic strategies that exploit the TNF-related apoptosis-inducing ligand (TRAIL)/TRAIL receptor pathway
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DOI：
10.1016/j.biocel.2006.10.005
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发表时间：
2007-01-01
影响因子：
4
通讯作者：
Smyth, Mark J.
中科院分区：
文献类型：
--
作者：
Cretney, Erika;Takeda, Kazuyoshi;Smyth, Mark J.
癌症是一种普遍的疾病，在美国，一半的男性和三分之一的女性在有生之年患上癌症。包括放射治疗、化疗和免疫治疗在内的许多癌症治疗的疗效是由于它们能够诱导肿瘤细胞凋亡。重组肿瘤坏死因子相关的凋亡诱导配体(TRAIL)选择性地诱导多种转化细胞的凋亡，但不能诱导大多数正常细胞的凋亡，因此目前正被开发为一种癌症治疗药物。针对人类死亡诱导TRAIL受体(DR4或DR5)的激动型单抗(MAbs)也在积极寻找。重要的是，在实验小鼠中，抗DR5的激动型rnAb与抗CD40和CD137的激动型单抗或IL-21或激动型单抗的联合治疗已观察到协同抗肿瘤作用。综上所述，这些发现表明，基于抗体的治疗会导致肿瘤细胞凋亡，并促进T细胞的记忆或功能，可能在抗癌方面有效。皇冠版权所有(C)2006由爱思唯尔有限公司出版。保留所有权利。
Cancer is a widespread disease, with half of all men and one-third of all women in the United States developing cancer during their lifetime. The efficacy of many cancer treatments including radiotherapy, chemotherapy and immunotherapy is due to their ability to induce tumor cell apoptosis. Recombinant tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is currently being developed as a cancer therapeutic since it selectively induces apoptosis in a variety of transformed cells, but not in most normal cells. Agonistic monoclonal antibodies (mAbs) specific for human death-inducing TRAIL receptors (DR4 or DR5) are also being actively pursued. Importantly, in experimental mice, synergistic anti-tumor effects have been observed with a combination treatment of agonistic rnAb against DR5 together with either IL-21 or agonistic mAbs against CD40 and CD137. Together, these findings suggest that antibody-based therapies that cause tumor cell apoptosis and promote T cell memory or function may be effective in fighting cancer. Crown Copyright (c) 2006 Published by Elsevier Ltd. All rights reserved.