Forero Andres, Lobuglio Albert F
Department of Medicine, Division of Hematology/Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, 35294-3300, USA.
Semin Oncol. 2003 Dec;30(6 Suppl 17):1-5. doi: 10.1053/j.seminoncol.2003.10.002.
Monoclonal antibodies (mAbs) were the first successful targeted therapy for cancer. In contrast to the nonspecific nature of most chemotherapy, antibodies bind with high specificity to cell-surface antigens, resulting in targeted killing of malignant cells, relative sparing of normal tissues, and low toxicity. Antibody therapy has undergone substantial development since Ehrlich's notion of a "magic bullet," in 1890. It was not until the 1970s, however, that mAbs became viable as therapeutic tools and clinical studies showed them to be effective. The results were most impressive in hematologic malignancies, especially B-cell non-Hodgkin's lymphoma. In 1997, rituximab (Rituxan; Genentech Inc, South San Francisco, CA, and Biogen Idec Inc, Cambridge, MA) became the first mAb approved by the US Food and Drug Administration for use in the treatment of cancer. The first approval for a radiolabeled antibody to treat cancer was in 2002 for (90)Y ibritumomab tiuxetan (Zevalin; Biogen Idec). This is a conjugate of an anti-CD20 mAb (ibritumomab, the murine parent of rituximab) with the beta-emitter radionuclide (90)Y. (90)Y ibritumomab tiuxetan has been shown to be safe and effective in the indicated patient population. Other radioimmunoconjugates are being investigated for the treatment of non-Hodgkin's lymphoma, as are several immunotoxins. This article reviews important events in the development of mAb therapy and radioimmunotherapy for B-cell non-Hodgkin's lymphoma.
单克隆抗体（mAb）是首个成功用于癌症治疗的靶向疗法。与大多数化疗的非特异性本质不同，抗体能高度特异性地结合细胞表面抗原，从而实现对恶性细胞的靶向杀伤，相对减少对正常组织的损伤，且毒性较低。自1890年埃利希提出“神奇子弹”的概念以来，抗体疗法取得了长足发展。然而，直到20世纪70年代，单克隆抗体才成为可行的治疗工具，临床研究表明其具有有效性。这一成果在血液系统恶性肿瘤，尤其是B细胞非霍奇金淋巴瘤中最为显著。1997年，利妥昔单抗（美罗华；基因泰克公司，加利福尼亚州南旧金山，以及百健艾迪公司，马萨诸塞州剑桥）成为首个获美国食品药品监督管理局批准用于癌症治疗的单克隆抗体。2002年，（90）钇伊布替膦（泽瓦林；百健艾迪）成为首个获批用于治疗癌症的放射性标记抗体。它是一种抗CD20单克隆抗体（伊布替膦，利妥昔单抗的鼠源亲本）与β发射体放射性核素（90）钇的偶联物。已证明（90）钇伊布替膦在特定患者群体中安全有效。其他放射免疫偶联物以及几种免疫毒素正在进行治疗非霍奇金淋巴瘤的研究。本文回顾了B细胞非霍奇金淋巴瘤单克隆抗体疗法和放射免疫疗法发展过程中的重要事件。
