Academic Department of Clinical Oncology, University of Nottingham, City Hospital, Hucknall Road, Nottingham, NG5 1PB, UK.
Expert Rev Vaccines. 2011 Jul;10(7):1093-106. doi: 10.1586/erv.11.33.
Monoclonal antibodies (mAbs) have an established role in current cancer therapy with seven approved for the treatment of a wide variety of tumors. The approved mAbs directly target tumor cells; however, it is becoming increasingly clear that as well as their direct effects, these mAbs can present antigens to the immune system. This stimulates long-lasting T-cell immunity, which may correlate with long-term survival. A more direct approach is to use mAbs to target antigens directly to antigen-presenting cells. One approach, ImmunoBody, which has just entered the clinic, stimulates antitumor immunity using mAbs genetically engineered to express tumor-specific T-cell epitopes. T cells not only respond via their T-cell receptors recognizing T-cell epitopes presented on MHC but are also influenced by stimulation of a wide variety of costimulatory molecules. mAbs targeting these molecules can also influence antitumor immunity. The main protagonist in this class of mAbs is ipilimumab, which has recently been shown to improve survival at 2 years in 23% of advanced melanoma patients. Combinations of mAbs targeting tumor antigens to activated antigen-presenting cells and mAbs targeting costimulatory receptors may provide effective therapy for a broad range of tumors.
单克隆抗体（mAbs）在当前的癌症治疗中具有重要作用，已有七种抗体被批准用于治疗多种肿瘤。这些已批准的 mAbs 直接针对肿瘤细胞；然而，越来越明显的是，除了直接作用外，这些 mAbs 还可以向免疫系统呈现抗原。这会刺激持久的 T 细胞免疫，这可能与长期生存相关。更直接的方法是使用 mAbs 将抗原直接靶向抗原呈递细胞。一种名为 ImmunoBody 的方法刚刚进入临床阶段，它使用经过基因工程改造以表达肿瘤特异性 T 细胞表位的 mAbs 来刺激抗肿瘤免疫。T 细胞不仅通过识别 MHC 上呈现的 T 细胞表位的 T 细胞受体做出反应，还受到各种共刺激分子的刺激的影响。针对这些分子的 mAbs 也可以影响抗肿瘤免疫。这类 mAbs 的主要代表是 ipilimumab，它最近被证明可以使 23%的晚期黑色素瘤患者的 2 年生存率提高。将靶向肿瘤抗原的 mAbs 与靶向激活的抗原呈递细胞的 mAbs 以及靶向共刺激受体的 mAbs 联合使用，可能为广泛的肿瘤提供有效的治疗方法。
