Martin Peter, Furman Richard R, Ruan Jia, Elstrom Rebecca, Barrientos Jacqueline, Niesvizky Ruben, Coleman Morton, Leonard John P
Center for Lymphoma and Myeloma, Division of Hematology-Oncology, Department of Medicine, Weill Cornell Medical College and New York Presbyterian Hospital, New York, NY 10021, USA.
Semin Hematol. 2008 Apr;45(2):126-32. doi: 10.1053/j.seminhematol.2008.02.007.
Over the past decade, the safety and efficacy of the anti-CD20 antibody rituximab has resulted in its use in virtually all patients with B-cell non-Hodgkin's lymphoma (NHL). Unfortunately, many patients who initially benefit from rituximab develop resistance while others may never respond. Both the successes and limitations of rituximab have heralded an explosion in research and development of novel monoclonal antibodies. Strategies employed to improve upon rituximab have included developing antibodies to target new epitopes of CD20 and new antigens, humanizing or creating fully human antibodies, and engineering antibodies with a potentially greater capacity for interaction with the host immune system. Each of these strategies has shown varying degrees of preclinical and clinical success. In this review we discuss the rationale for various strategies and report results from clinical trials employing these agents.
在过去十年中,抗CD20抗体利妥昔单抗的安全性和有效性使其几乎被用于所有B细胞非霍奇金淋巴瘤(NHL)患者。不幸的是,许多最初从利妥昔单抗治疗中获益的患者会产生耐药性,而其他患者可能根本没有反应。利妥昔单抗的成功与局限性都预示着新型单克隆抗体研发的蓬勃发展。为改进利妥昔单抗所采用的策略包括开发针对CD20新表位和新抗原的抗体、对抗体进行人源化或制备完全人源抗体,以及构建与宿主免疫系统相互作用能力可能更强的抗体。这些策略均已在不同程度上取得了临床前和临床研究的成功。在本综述中,我们将讨论各种策略的原理,并报告使用这些药物的临床试验结果。