Grillo-López A J
Medical and Regulatory Affairs Division, IDEC Pharmaceuticals Corporation, San Diego, CA 92121, USA.
Semin Oncol. 2000 Dec;27(6 Suppl 12):9-16.
Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC Pharmaceutical Corporation, San Diego, CA) is a unique monoclonal antibody for the treatment of non-Hodgkin's lymphoma. This chimeric mouse/human antibody was discovered in 1991 at IDEC Pharmaceuticals' laboratories, where the antibody was genetically engineered and produced utilizing high-yield expression systems. It is a human IgG1 kappa antibody with mouse variable regions isolated from a murine anti-CD20 antibody, IDEC-2B8, that binds with high affinity to cells expressing the CD20 antigen found on the surface of malignant and normal B cells, but not on other normal tissues. It mediates complement-dependent cell lysis in the presence of human complement, and antibody-dependent cellular cytotoxicity with human effector cells. Also, it has been shown to induce apoptosis and to sensitize chemoresistant human lymphoma cell lines in vitro. Clinical development was expedited (3 years) with the first patient entered in phase I trials in March 1993 and the last patient entered in the phase III study in March 1996. IDEC Pharmaceuticals began a collaboration with Genentech, Inc in March 1995 and with F. Hoffman-LaRoche (Nutley, NJ) shortly thereafter. Marketing approval was granted by the US Food and Drug Administration on November 26, 1997 (and by the European Union on June 2, 1998) for the indication of relapsed or refractory, CD20-positive, B-cell, low-grade or follicular non-Hodgkin's lymphoma. Rituximab is the first therapeutic monoclonal antibody approved for the treatment of cancer and the first single agent approved specifically for therapy for a lymphoma. Substantial research has been performed over the past 8 years to further the understanding of this novel therapeutic. Nevertheless, much remains to be accomplished in key areas such as mechanism of action and resistance, combinations with chemotherapy, biologics and radiotherapy/radioimmunotherapy, role within multimodality regimens, and nonmalignant applications. Research conducted in the coming years should be targeted toward resolving these important issues.
利妥昔单抗（美罗华；基因泰克公司，加利福尼亚州南旧金山和IDEC制药公司，加利福尼亚州圣地亚哥）是一种用于治疗非霍奇金淋巴瘤的独特单克隆抗体。这种嵌合型鼠/人抗体于1991年在IDEC制药公司的实验室中发现，在那里该抗体通过基因工程技术利用高产表达系统生产。它是一种人IgG1κ抗体，其鼠源可变区分离自鼠抗CD20抗体IDEC-2B8，该抗体与表达于恶性和正常B细胞表面但不在其他正常组织上的CD20抗原的细胞具有高亲和力结合。在人补体存在的情况下，它介导补体依赖性细胞裂解，并与人类效应细胞产生抗体依赖性细胞毒性。此外，已证明它在体外可诱导凋亡并使化疗耐药的人淋巴瘤细胞系敏感。临床开发进程加快（3年），首例患者于1993年3月进入I期试验，最后一例患者于1996年3月进入III期研究。1995年3月，IDEC制药公司开始与基因泰克公司合作，此后不久又与F. 霍夫曼 - 罗氏公司（新泽西州纳特利）合作。1997年11月26日，美国食品药品监督管理局批准其上市（1998年6月2日欧盟也批准其上市），用于治疗复发或难治性、CD20阳性、B细胞、低度或滤泡性非霍奇金淋巴瘤。利妥昔单抗是首个被批准用于治疗癌症的治疗性单克隆抗体，也是首个专门被批准用于淋巴瘤治疗的单一药物。在过去8年中进行了大量研究以进一步了解这种新型治疗方法。然而，在作用机制和耐药性、与化疗、生物制剂及放疗/放射免疫疗法的联合应用、多模式治疗方案中的作用以及非恶性应用等关键领域仍有许多工作要做。未来几年开展的研究应致力于解决这些重要问题。
