Goldenberg David M
Garden State Cancer Center, Center for Molecular Medicine and Immunology 520 Belleville Avenue, Belleville, New Jersey 07109, USA.
Expert Rev Anticancer Ther. 2006 Oct;6(10):1341-53. doi: 10.1586/14737140.6.10.1341.
B cells play an important role in the pathogenesis of certain lymphomas and leukemias, as well as many autoimmune diseases. Antagonistic B-cell antibodies are thus gaining an increasing role in the management of these diseases. The first antibody target in this regard was CD20, with the development and introduction of rituximab in the management of B-cell malignancies, as well as rheumatoid arthritis. A second candidate target is CD22. The first antagonistic antibody to this B-cell marker, epratuzumab, appears to function, in contrast to CD20 antibodies, more by modulation of B cells rather than by their high depletion in circulation. Originally developed for the treatment of non-Hodgkin's lymphoma, epratuzumab has now been found to be effective, with a very good safety profile, in two prototype autoimmune diseases: systemic lupus erythematosus and primary Sjögren's syndrome. Recent studies have demonstrated the activity and safety of epratuzumab in non-Hodgkin's lymphoma patients who have relapsed or are refractive to conventional therapy, including rituximab, and has also shown good activity in follicular and diffuse large B-cell lymphoma in combination with rituximab. As such, this new investigative antibody may have a significant market potential owing to the multitude of diseases and patients who may benefit from a CD22, B-cell antibody immunotherapy that is complementary to the known effects and role of CD20 antibodies, but can usually be administered within 1 h and depletes approximately 50% of circulating B cells.
B细胞在某些淋巴瘤和白血病以及许多自身免疫性疾病的发病机制中发挥着重要作用。因此,拮抗B细胞抗体在这些疾病的治疗中发挥着越来越重要的作用。在这方面,第一个抗体靶点是CD20,随着利妥昔单抗的研发和引入,其可用于治疗B细胞恶性肿瘤以及类风湿性关节炎。第二个候选靶点是CD22。与CD20抗体相比,针对这种B细胞标志物的首个拮抗抗体——依帕珠单抗,似乎更多地是通过调节B细胞发挥作用,而非使循环中的B细胞大量耗竭。依帕珠单抗最初是为治疗非霍奇金淋巴瘤而研发的,现已发现其在两种典型的自身免疫性疾病——系统性红斑狼疮和原发性干燥综合征中有效,且安全性良好。最近的研究表明,依帕珠单抗在复发或对包括利妥昔单抗在内的传统疗法耐药的非霍奇金淋巴瘤患者中具有活性和安全性,并且在与利妥昔单抗联合使用时,对滤泡性和弥漫性大B细胞淋巴瘤也显示出良好的活性。因此,这种新型研究性抗体可能具有巨大的市场潜力——众多疾病和患者可能会受益于一种CD22 B细胞抗体免疫疗法,该疗法与CD20抗体的已知作用互补,但通常可在1小时内给药,并可使约50%的循环B细胞耗竭。