Mechanisms of killing by anti-CD20 monoclonal antibodies
Mechanisms of killing by anti-CD20 monoclonal antibodies
复制标题
DOI：
10.1016/j.molimm.2007.06.151
复制
发表时间：
2007-09-01
影响因子：
3.6
通讯作者：
Taylor, Ronald P.
中科院分区：
文献类型：
--
作者：
Glennie, Martin J.;French, Ruth R.;Taylor, Ronald P.
CD 20是在成熟B细胞和大多数恶性B细胞上表达的细胞表面标志物，但不是干细胞或浆细胞。它是单克隆抗体（mAb）（如利妥昔单抗和奥法木单抗）的理想靶标，因为它在大多数B细胞恶性肿瘤中以高水平表达，但在mAb治疗后不会内化或从质膜脱落。这允许mAb在细胞表面上持续延长的时间，并从补体和表达FcR的先天效应物（特别是巨噬细胞）递送持续的免疫攻击。当与某些mAb结合时，CD 20也可以产生跨膜信号，尽管未经证实，但这可能提供抗CD 20 mAb治疗成功的重要因素。这些有利的特征导致抗-CD 20 mAb被开发和开发用于免疫治疗，其中它们已被证明通过分别删除恶性或正常B细胞在恶性疾病和自身免疫性疾病的治疗中显著有效。在这篇综述中，我们讨论了这些mAb在过去十年中如何推动免疫治疗领域的研究，详细介绍了它们可能的作用模式及其在效应物耗竭方面的局限性，并探讨了它们在未来可能被增强和进一步利用的方法。(c)2007爱思唯尔有限公司版权所有。
CD20 is a cell-surface marker expressed on mature B cells and most malignant B cells, but not stem or plasma cells. It is an ideal target for monoclonal antibodies (mAb), such as rituximab and ofatumumab, as it is expressed at high levels on most B-cell malignancies, but does not become internalized or shed from the plasma membrane following mAb treatment. This allows mAb to persist on the cell surface for extended periods and deliver sustained immunological attack from complement and FcR-expressing innate effectors, particularly macrophages. CD20 can also generate transmembrane signals when engaged by certain mAb which, although unproven, might provide an important element of the therapeutic success of anti-CD20 mAb. These favourable characteristics have led to anti-CD20 mAb being developed and exploited for use in immunotherapy, where they have proven remarkably efficacious in both the treatment of malignant disease and autoimmune disorders by deleting malignant or normal B cells, respectively. In this review, we discuss how these mAb have driven research in the immunotherapy field over the last decade, detail their likely modes of action and their limitations in terms of effector exhaustion, and explore ways in which they might be enhanced and further exploited in the future. (c) 2007 Elsevier Ltd. All rights reserved.