Jefford M, Maraskovsky E, Cebon J, Davis I D
Ludwig Institute for Cancer Research, Melbourne, Victoria, Australia.
Lancet Oncol. 2001 Jun;2(6):343-53. doi: 10.1016/s1470-2045(00)00389-2.
Although the immune system evolved to protect the host from infection, what fires the popular imagination is its potential to recognise and destroy cancer. The immune system can generate potent cytotoxicity (eg transplant rejection), but can these mechanisms be harnessed for therapeutic benefit in patients with cancer? The discovery of an ever-increasing array of tumour antigens shows clearly that the targets exist. The challenge lies in generating a sufficiently potent response towards them. Central to the processes of antigen recognition, processing, and presentation to the immune system are dendritic cells. Understanding of the relation between these and the cellular immune response is crucial to elucidation of how to manipulate immune responses. The past 20 years have witnessed a dramatic expansion in this understanding and led to the first early-phase clinical trials of dendritic cells for the treatment of cancer. These studies have established the safety and feasibility of this approach and have produced encouraging evidence of therapeutic efficacy. This paper reviews the biology of dendritic cells and their use in clinical trials, as well as highlighting issues for future trial design.
尽管免疫系统的进化是为了保护宿主免受感染,但激发大众想象力的是其识别和摧毁癌症的潜力。免疫系统能够产生强大的细胞毒性(如移植排斥反应),但这些机制能否用于癌症患者的治疗并带来益处呢?越来越多肿瘤抗原的发现清楚地表明靶点是存在的。挑战在于对这些靶点产生足够强大的反应。树突状细胞是抗原识别、处理以及呈递给免疫系统过程的核心。了解它们与细胞免疫反应之间的关系对于阐明如何操控免疫反应至关重要。在过去20年里,这方面的认识有了显著扩展,并催生了首批用于治疗癌症的树突状细胞早期临床试验。这些研究证实了这种方法的安全性和可行性,并产生了令人鼓舞的治疗效果证据。本文综述了树突状细胞的生物学特性及其在临床试验中的应用,同时突出了未来试验设计中存在的问题。