White C A, Weaver R L, Grillo-López A J
IDEC Pharmaceuticals Corporation, 3030 Callan Road, San Diego, California 92121; e-mail:
Annu Rev Med. 2001;52:125-45. doi: 10.1146/annurev.med.52.1.125.
Despite testing since the mid-1900s, only in the past three years have some monoclonal antibodies provided sufficient efficacy and safety data to support regulatory approval as cancer therapy. Adjuvant-edrecolomab monoclonal antibody was approved in Germany after demonstration of a statistically significant 32% improvement over observation alone in the seven-year mortality rate for patients with colorectal cancer. Similarly, trastuzumab monoclonal antibody combined with chemotherapy prolonged the median time to the progression of breast cancer compared to chemotherapy alone. Unconjugated monoclonal antibodies investigated for the treatment of hematologic malignancies include anti-idiotype, CAMPATH-1, and rituximab. Rituximab was the first such therapy approved in the United States for relapsed or refractory low-grade or follicular B-cell non-Hodgkin's lymphoma after demonstration of an overall response rate of 48% and a duration of response of 11.7 months. The radioisotope-conjugated monoclonal antibodies tested as therapy include anti-B1, LYM-1, LL2, anti-CD33, and ibritumomab tiuxetan. Clearly, the full potential of immunotherapy still lies ahead.
自20世纪中叶以来一直在进行相关测试,但直到过去三年,一些单克隆抗体才提供了足够的疗效和安全性数据来支持其作为癌症治疗药物获得监管批准。在证明接受佐剂性爱地西单抗单克隆抗体治疗的结直肠癌患者的七年死亡率比单纯观察有统计学上显著的32%的改善后,该药物在德国获得批准。同样,与单纯化疗相比,曲妥珠单抗单克隆抗体联合化疗延长了乳腺癌进展的中位时间。研究用于治疗血液系统恶性肿瘤的非偶联单克隆抗体包括抗独特型抗体、CAMPATH-1和利妥昔单抗。在证明总体缓解率为48%且缓解持续时间为11.7个月后,利妥昔单抗成为美国首个获批用于复发或难治性低度或滤泡性B细胞非霍奇金淋巴瘤的此类疗法。作为治疗手段进行测试的放射性同位素偶联单克隆抗体包括抗B1、LYM-1、LL2、抗CD33和替伊莫单抗。显然,免疫疗法的全部潜力仍有待挖掘。