Cragg Mark S, Walshe Claire A, Ivanov Andrey O, Glennie Martin J
Tenovus Research Laboratory, Cancer Sciences Division, Southampton University, Southampton General Hospital, Southampton, UK.
Curr Dir Autoimmun. 2005;8:140-74. doi: 10.1159/000082102.
CD20 is a 33-37 kDa, non-glycosylated phosphoprotein expressed on the surface of almost all normal and malignant B cells. It is also the target for rituximab, the most effective anti-cancer monoclonal antibody developed to date. Rituximab has now been given to over 300,000 lymphoma patients in the last decade and interestingly is now being explored for use in other disorders, such as autoimmune conditions including rheumatoid arthritis and systemic lupus erythematosus. Despite the success in immunotherapy, knowledge about the biology of CD20 is still relatively scarce, partly because it has no known natural ligand and CD20 knockout mice display an almost normal phenotype. However, interesting insight has come from work showing that CD20 is resident in lipid raft domains of the plasma membrane where it probably functions as a store-operated calcium channel following ligation of the B cell receptor for antigen. In the current review, these and data relating to its activity as a therapeutic target will be discussed in depth. It is clear that a greater understanding of CD20 biology and the effector mechanisms, such as antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and growth regulation, which operate with anti-CD20 mAb in vivo will allow more efficient exploitation of CD20 as a therapeutic target.
CD20是一种33 - 37 kDa的非糖基化磷蛋白，几乎在所有正常和恶性B细胞表面均有表达。它也是利妥昔单抗的作用靶点，利妥昔单抗是迄今为止研发出的最有效的抗癌单克隆抗体。在过去十年中，已有超过30万名淋巴瘤患者接受了利妥昔单抗治疗，有趣的是，目前正在探索其在其他疾病中的应用，如包括类风湿性关节炎和系统性红斑狼疮在内的自身免疫性疾病。尽管免疫治疗取得了成功，但关于CD20生物学特性的了解仍然相对较少，部分原因是它没有已知的天然配体，且CD20基因敲除小鼠表现出几乎正常的表型。然而，有趣的见解来自于研究表明CD20存在于质膜的脂筏结构域中，在抗原与B细胞受体结合后，它可能作为一种储存性钙通道发挥作用。在本综述中，将深入讨论这些内容以及与其作为治疗靶点的活性相关的数据。显然，更深入地了解CD20生物学特性以及诸如抗体依赖性细胞毒性、补体依赖性细胞毒性和生长调节等效应机制（这些机制在体内与抗CD20单克隆抗体共同发挥作用）将有助于更有效地将CD20用作治疗靶点。
