Weiner L M
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Semin Oncol. 1999 Aug;26(4 Suppl 12):41-50.
Monoclonal antibody-based therapeutics are beginning to realize the promise that was predicted with the advent of the core technology more than 20 years ago. Antibody-based therapeutics targeting tumor cell surface antigens such as B-cell idiotypes, CD20 on malignant B cells, CD33 on leukemic blasts, and HER2/neu on breast cancer cells have shown efficacy in clinical trials. Multiple antibody-based strategies have shown promising efficacy in recent clinical trials. Unconjugated immunoglobulins directed against CD20 induce partial and complete responses in up to 50% of patients with advanced, indolent non-Hodgkin's lymphoma When such antibodies are conjugated to appropriate radionuclides and administered in therapeutic doses, the proportions of complete and overall responses increase considerably. Conjugates composed of anti-CD33 antibodies and the chemotherapy agent, calicheamicin, show promising activity in patients with relapsed or refractory acute myelogenous leukemia. Treatment of patients with advanced breast cancer using the anti-HER2/neu antibody trastuzumab (Herceptin; Genentech, San Francisco) leads to objective responses in some patients whose tumors overexpress the HER2/neu oncoprotein. These exciting results justify recent enthusiasm for continued efforts to refine existing approaches and to develop new antibody-based strategies to treat human malignancy.
基于单克隆抗体的治疗方法正开始实现20多年前随着核心技术问世而被预测的前景。靶向肿瘤细胞表面抗原的基于抗体的治疗方法，如B细胞独特型、恶性B细胞上的CD20、白血病原始细胞上的CD33以及乳腺癌细胞上的HER2/neu，在临床试验中已显示出疗效。多种基于抗体的策略在近期临床试验中已显示出有前景的疗效。针对CD20的未偶联免疫球蛋白在高达50%的晚期惰性非霍奇金淋巴瘤患者中诱导部分和完全缓解。当此类抗体与合适的放射性核素偶联并以治疗剂量给药时，完全缓解和总体缓解的比例会大幅增加。由抗CD33抗体和化疗药物加利车霉素组成的偶联物在复发或难治性急性髓性白血病患者中显示出有前景的活性。使用抗HER2/neu抗体曲妥珠单抗（赫赛汀；基因泰克公司，旧金山）治疗晚期乳腺癌患者，会使一些肿瘤过度表达HER2/neu癌蛋白的患者产生客观缓解。这些令人振奋的结果证明了近期人们对持续努力改进现有方法以及开发新的基于抗体的策略来治疗人类恶性肿瘤的热情是合理的。
