Zangemeister-Wittke Uwe
Department of Pharmacology, University of Bern, Bern, Switzerland.
Pathobiology. 2005;72(6):279-86. doi: 10.1159/000091325.
The efficacy of traditional anti-cancer agents comes with the price of toxicity to normal cells, which limits the success of therapy. In the past 2 decades, greater understanding of the molecular differences between malignant and normal cells has led to the development of therapies that more specifically target human tumors. These include new anti-cancer agents directed against intracellular targets associated with malignant alterations, such as increased proliferation, impaired apoptosis or angiogenesis. In addition, antibodies have been developed that are directed towards tumor-associated antigens and provide tailor-made effector functions by inhibiting cell growth, inducing apoptosis or constituting cytotoxic drug delivery systems. Since the targeted approach of anti-cancer therapies increases the exposure of malignant cells and at the same time reduces the exposure of normal tissues, it offers the promise of enhanced efficacy and lower side effects. Antibodies, immunoconjugates and liposomal drug delivery systems derived thereof are now mainstream cancer therapeutics, and by the end of 2003 17 marketed antibody-based products generated several billion in combined annual sales. This study highlights the most recent breakthroughs in antibody technology and summarizes major achievements in antibody-based cancer therapy in oncology trials.
传统抗癌药物在发挥疗效的同时，会对正常细胞产生毒性，这限制了治疗的效果。在过去20年里，对恶性细胞与正常细胞分子差异的深入了解促使了更具针对性地靶向人类肿瘤的治疗方法的发展。这些方法包括针对与恶性改变相关的细胞内靶点的新型抗癌药物，比如增殖增加、凋亡受损或血管生成异常。此外，还研发出了针对肿瘤相关抗原的抗体，这些抗体通过抑制细胞生长、诱导凋亡或构建细胞毒性药物递送系统来发挥定制的效应功能。由于抗癌治疗的靶向方法增加了恶性细胞的暴露量，同时减少了正常组织的暴露量，因此有望提高疗效并降低副作用。抗体、免疫缀合物及其衍生的脂质体药物递送系统如今已成为主流的癌症治疗手段，截至2003年底，17种已上市的基于抗体的产品年销售额总计达数十亿美元。本研究着重介绍了抗体技术的最新突破，并总结了肿瘤学试验中基于抗体的癌症治疗的主要成果。
