Cretney Erika, Takeda Kazuyoshi, Smyth Mark J
Cancer Immunology Program, Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Vic., 3002, Australia.
Int J Biochem Cell Biol. 2007;39(2):280-6. doi: 10.1016/j.biocel.2006.10.005. Epub 2006 Oct 7.
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 mAb 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.
癌症是一种广泛存在的疾病，在美国，有一半的男性和三分之一的女性在其一生中会患上癌症。包括放疗、化疗和免疫疗法在内的许多癌症治疗方法的疗效，都归因于它们诱导肿瘤细胞凋亡的能力。重组肿瘤坏死因子（TNF）相关凋亡诱导配体（TRAIL）目前正作为一种癌症治疗药物进行研发，因为它能选择性地诱导多种转化细胞凋亡，但对大多数正常细胞无此作用。针对人类死亡诱导TRAIL受体（DR4或DR5）的激动性单克隆抗体（mAb）也在积极研发中。重要的是，在实验小鼠中，已观察到抗DR5激动性mAb与IL-21或抗CD40和CD137激动性mAb联合治疗具有协同抗肿瘤作用。这些发现共同表明，基于抗体的疗法，即能诱导肿瘤细胞凋亡并促进T细胞记忆或功能的疗法，可能在对抗癌症方面有效。
