Gray Juliet C, Johnson Peter W M, Glennie Martin J
Cancer Research UK Medical Oncology Unit, The Cancer Sciences Division, Southampton University School of Medicine, General Hospital, Southampton SO16 6YD, UK.
Clin Sci (Lond). 2006 Aug;111(2):93-106. doi: 10.1042/CS20060024.
The aim of cancer immunotherapy is to employ the specificity of the immune system to provide a more effective, less toxic, treatment compared with conventional therapies. Although many strategies have been used to try to generate effective anticancer immune responses, very few have reached mainstream clinical use. A new approach introduced over the last few years is to use immunostimulatory mAbs (monoclonal antibodies) to boost weak endogenous antitumour immune responses to levels which are therapeutic. Such agonistic or antagonistic mAbs bind to key receptors in the immune system acting to enhance antigen presentation, provide co-stimulation or to counteract immunoregulation. In animal models, this approach has been shown to promote powerful tumour-specific T-cell responses capable of clearing established tumour and leaving the animal with long-term immunity. In addition to this impressive therapy seen in tumour models, these same mAbs also have the potential to be therapeutically useful in autoimmune and infectious diseases. This review discusses the use of these mAbs as therapeutic agents, their advantages and disadvantages and the challenges that need to be overcome to use them clinically.
癌症免疫疗法的目的是利用免疫系统的特异性,提供一种与传统疗法相比更有效、毒性更小的治疗方法。尽管已经采用了许多策略来试图产生有效的抗癌免疫反应,但很少有策略进入主流临床应用。在过去几年中引入的一种新方法是使用免疫刺激单克隆抗体(mAb),将微弱的内源性抗肿瘤免疫反应增强到治疗水平。这种激动性或拮抗性单克隆抗体与免疫系统中的关键受体结合,作用是增强抗原呈递、提供共刺激或抵消免疫调节。在动物模型中,这种方法已被证明能促进强大的肿瘤特异性T细胞反应,能够清除已形成的肿瘤,并使动物获得长期免疫力。除了在肿瘤模型中看到的这种令人印象深刻的疗法外,这些相同的单克隆抗体在自身免疫性疾病和感染性疾病中也有可能具有治疗作用。本综述讨论了这些单克隆抗体作为治疗剂的用途、它们的优缺点以及在临床应用中需要克服的挑战。