Cretney Erika, Shanker Anil, Yagita Hideo, Smyth Mark J, Sayers Thomas J
Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Immunol Cell Biol. 2006 Feb;84(1):87-98. doi: 10.1111/j.1440-1711.2005.01413.x.
Recombinant, soluble TNF-related apoptosis-inducing ligand (TRAIL) is currently being developed as a promising natural immune molecule for trial in cancer patients because it selectively induces apoptosis in transformed or stressed cells but not in most normal cells. In cancer patients, phase 1 and 2 clinical trials using agonistic mAbs that engage the human TRAIL receptors DR4 and DR5 have also provided encouraging results. It is now evident that TRAIL suppresses autoimmune disease in various experimental animal models, suggesting that the therapeutic value of recombinant TRAIL and agonistic DR4 and DR5 mAbs might also extend to the suppression of autoimmune disease. This review provides an insight into our current understanding of the role(s) of TRAIL in disease, with a specific focus on cancer and autoimmunity. We also emphasize biological agents and drugs that sensitize tumour cells to TRAIL-mediated apoptosis and discuss the potential molecular basis for their sensitization.
重组可溶性肿瘤坏死因子相关凋亡诱导配体（TRAIL）目前正作为一种有前景的天然免疫分子进行研发，用于癌症患者的试验，因为它能选择性地诱导转化细胞或应激细胞凋亡，而在大多数正常细胞中则不会。在癌症患者中，使用激活人TRAIL受体DR4和DR5的激动性单克隆抗体进行的1期和2期临床试验也取得了令人鼓舞的结果。现在很明显，TRAIL在各种实验动物模型中能抑制自身免疫性疾病，这表明重组TRAIL以及激动性DR4和DR5单克隆抗体的治疗价值可能也延伸至自身免疫性疾病的抑制。本综述深入探讨了我们目前对TRAIL在疾病中的作用的理解，特别关注癌症和自身免疫。我们还强调了使肿瘤细胞对TRAIL介导的凋亡敏感的生物制剂和药物，并讨论了它们产生敏感性的潜在分子基础。
