Lee Steve C, López-Albaitero Andrés, Ferris Robert L
The Hillman Cancer Center Research Pavilion, 5117 Centre Avenue, Room 2.26b, Pittsburgh, PA 15213, USA.
Curr Oncol Rep. 2009 Mar;11(2):156-62. doi: 10.1007/s11912-009-0023-5.
Monoclonal antibodies (mAbs) are now commonly used therapeutic agents in cancer patients. Since US Food and Drug Administration approval of cetuximab for head and neck squamous cell carcinoma, it has been used increasingly in this disease. Several other mAbs also are in development or in clinical -trials. Recently, evidence has accumulated that mAbs induce activation of cellular immunity, including natural killer and T cells and that this may contribute to clinical response. mAbs have been shown to mediate antibody-dependent cellular cytotoxicity, complement-dependent lysis, and activation of tumor antigen-specific T cells. Various patient and tumor factors, such as polymorphisms in Fcgamma receptors expressed by immune cells, activity of T-regulatory cells, and tumor escape through downregulation of antigen-processing machinery in tumor cells, are likely to modulate the immune activation mediated by therapeutic mAbs. Understanding the interplay of these factors is likely to improve the selection of the most appropriate candidates for mAb-based immunotherapy, prediction of clinical response, and our understanding of mechanisms of tumor escape from therapeutic mAbs.
单克隆抗体（mAbs）如今是癌症患者常用的治疗药物。自美国食品药品监督管理局批准西妥昔单抗用于治疗头颈部鳞状细胞癌以来，该药在该疾病治疗中的应用日益广泛。其他几种单克隆抗体也正处于研发或临床试验阶段。最近，越来越多的证据表明，单克隆抗体可诱导包括自然杀伤细胞和T细胞在内的细胞免疫激活，这可能对临床疗效有促进作用。单克隆抗体已被证明可介导抗体依赖的细胞毒性作用、补体依赖的细胞溶解作用以及肿瘤抗原特异性T细胞的激活。各种患者和肿瘤因素，如免疫细胞表达的Fcγ受体多态性、T调节细胞的活性以及肿瘤细胞通过下调抗原加工机制实现的肿瘤逃逸，都可能调节治疗性单克隆抗体介导的免疫激活。了解这些因素之间的相互作用，可能会改善基于单克隆抗体的免疫疗法最合适候选者的选择、临床疗效的预测，以及我们对肿瘤逃避治疗性单克隆抗体机制的理解。
