Bhat S A, Czuczman M S
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.
Neth J Med. 2009 Sep;67(8):311-21.
Monoclonal antibodies (mAbs) have revolutionised the treatment of malignancies, especially non-Hodgkin's lymphoma (NHL). Antibody-based therapies target tumour cells expressing a specific antigen while sparing the majority of normal cells leading to a decrease in treatment-associated toxicity. Rituximab, a monoclonal antibody directed against CD20 on B cells, was the first monoclonal antibody to be approved by the US Food and Drug Association (FDA) in 1997 for the treatment of patients with relapsed/refractory, follicular or low-grade NHL . However, it was soon realised that not all patients respond to rituximab therapy and close to 60% of patients with follicular lymphoma who were previously sensitive to rituximab become 'resistant' to repeat rituximab therapy. This led to further attempts to improve the antitumour activity of anti-CD20 mAbs (i.e. 2nd/3rd generation anti-CD20s), and to identify additional potential targets on lymphoma cells other than CD20. A number of these antibodies directed against lymphoma cell targets other than CD20 are now undergoing development, many of which are currently in clinical trials. This manuscript focuses on an overview of these 'non-anti-CD20' novel mAbs for NHL.
单克隆抗体(mAb)彻底改变了恶性肿瘤的治疗方式,尤其是非霍奇金淋巴瘤(NHL)。基于抗体的疗法靶向表达特定抗原的肿瘤细胞,同时使大多数正常细胞免受影响,从而降低了治疗相关毒性。利妥昔单抗是一种针对B细胞上CD20的单克隆抗体,于1997年成为首个获得美国食品药品监督管理局(FDA)批准用于治疗复发/难治性、滤泡性或低级NHL患者的单克隆抗体。然而,很快人们就意识到并非所有患者都对利妥昔单抗治疗有反应,之前对利妥昔单抗敏感的滤泡性淋巴瘤患者中,近60%对重复使用利妥昔单抗治疗产生“耐药”。这促使人们进一步尝试提高抗CD20单克隆抗体(即第二代/第三代抗CD20抗体)的抗肿瘤活性,并在淋巴瘤细胞上寻找除CD20之外的其他潜在靶点。目前,许多针对CD20以外淋巴瘤细胞靶点的抗体正在研发中,其中不少正处于临床试验阶段。本文着重概述这些用于NHL的“非抗CD20”新型单克隆抗体。