Qu Yu-Hua, Li Yang
Department of Pediatrics, Sun Yet-Sen Memorial Hospital, Sun Yet-Sen University, Guangzhou 510120, Guangdong Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2010 Oct;18(5):1370-5.
In recent years, as increasing of monoclonal antibody application in clinic, the antitumor effect of antibody dependent cell-mediated cytotoxicity (ADCC) get increasing attention. The natural killer (NK) cells are the most important effector cells mediating specific antitumor of ADCC; the phagocytes, T-cells and granulocytes have the definite effect on antitumor of ADCC. ADCC is confirmed as the important mechanism and means for clinically treating the cancers with monoclonal antibodies. The IgG antibody firstly combines with target cells (tumor cells) through antigen-binding sites, and then FcγR on effector cells identifies its Fc fragment and mediates ADCC. Today many kinds of monoclonal antibodies have been put into clinical application such as rituximab and other new anti-CD20 monoclonal antibodies including trastuzumab, erbitux, cetuximab, edrecolomab, nimotuzumab, gemtuzumab ozogamicin and so on, which all can mediate ADCC. The antitumor effects of ADCC mediated by monoclonal antibody can be influenced by IgG Fc receptor gene polymorphism, tumor cell antigen, serum antibody levels, cytokines and drugs etc. As to peripheral blood mononuclear cells, ADCC efficacies of FcγRIIIa-158V/V and FcγRIIa-131H/H are higher than that of other genotypes, while increasing the level of tumor antigen and decreasing the level of serum antibody or adding some cytokines (IL-2, IL-21, IL-15, etc) may elevate the ADCC effect mediated by monoclonal antibodies. Avoiding use of certain drugs (dexamethasone, TNF antagonist) or appropriately using of ondansetron and clemastine also can enhance the anti-tumor effect of ADCC mediated by monoclonal antibodies. In short, ADCC is very important in clinical application for anti-tumor treatment, but its efficacy may be impacted by multiple factors.In this article, the killing mechanisms of ADCC, the clinical use of monoclonal antibodies with antitumor effect of ADCC, the factors influencing anti-tumor efficacy of ADCC, and the antitumor effects of ADCC by other cells are reviewed.
近年来，随着单克隆抗体在临床上的应用日益增多，抗体依赖的细胞介导的细胞毒性作用（ADCC）的抗肿瘤效应受到越来越多的关注。自然杀伤（NK）细胞是介导ADCC特异性抗肿瘤的最重要效应细胞；吞噬细胞、T细胞和粒细胞对ADCC的抗肿瘤作用也有一定影响。ADCC被确认为临床上用单克隆抗体治疗癌症的重要机制和手段。IgG抗体首先通过抗原结合位点与靶细胞（肿瘤细胞）结合，然后效应细胞上的FcγR识别其Fc片段并介导ADCC。如今，多种单克隆抗体已投入临床应用，如利妥昔单抗以及其他新型抗CD20单克隆抗体，包括曲妥珠单抗、爱必妥、西妥昔单抗、依得利单抗、尼妥珠单抗、吉妥珠单抗奥唑米星等，它们均能介导ADCC。单克隆抗体介导的ADCC的抗肿瘤效应可受IgG Fc受体基因多态性、肿瘤细胞抗原、血清抗体水平、细胞因子和药物等影响。对于外周血单个核细胞，FcγRIIIa - 158V/V和FcγRIIa - 131H/H的ADCC效能高于其他基因型，而提高肿瘤抗原水平、降低血清抗体水平或添加某些细胞因子（IL - 2、IL - 21、IL - 15等）可能会提高单克隆抗体介导的ADCC效应。避免使用某些药物（地塞米松、TNF拮抗剂）或适当使用昂丹司琼和氯马斯汀也可增强单克隆抗体介导的ADCC的抗肿瘤作用。总之，ADCC在抗肿瘤治疗的临床应用中非常重要，但其疗效可能受到多种因素的影响。本文综述了ADCC的杀伤机制、具有ADCC抗肿瘤作用的单克隆抗体的临床应用、影响ADCC抗肿瘤疗效的因素以及其他细胞介导的ADCC的抗肿瘤作用。
