Farah R A, Clinchy B, Herrera L, Vitetta E S
Cancer Immunobiology Center, University of Texas Southwestern Medical Center at Dallas 75235-8576, USA.
Crit Rev Eukaryot Gene Expr. 1998;8(3-4):321-56. doi: 10.1615/critreveukargeneexpr.v8.i3-4.50.
Monoclonal antibodies (Mabs) were first described by Köhler and Milstein in 1975. Not only did this discovery lead to a Nobel prize, but it created an enormous scientific field that has now become a multimillion dollar industry. Mabs made the transition from laboratory reagents to clinical diagnostics very quickly. However, their development as therapeutic agents was, as predicted, more costly and time-consuming. Indeed, clinicians and scientists were required to learn a new set of rules for using these large, immunogenic, targeted agents in humans. Nevertheless, in 1997 the first Mab was licensed in the U.S. and several others will soon follow. In this review, we discuss Mab-based strategies for the treatment of cancer. We compare native, fragmented, recombinant and chimeric antibodies, bispecific antibodies, immunoconjugates, and immunoliposomes. The rationale for their development, their advantages, their in vitro and in vivo performance, and their clinical usefulness are discussed.
单克隆抗体(Mabs)于1975年首次由科勒和米尔斯坦描述。这一发现不仅荣获了诺贝尔奖,还开创了一个庞大的科学领域,如今已发展成为一个价值数百万美元的产业。单克隆抗体迅速从实验室试剂转变为临床诊断工具。然而,正如预期的那样,其作为治疗药物的开发成本更高、耗时更长。实际上,临床医生和科学家需要学习一套全新的规则,以便在人体中使用这些大型、具有免疫原性的靶向药物。尽管如此,1997年第一种单克隆抗体在美国获得许可,其他几种也将很快获批。在本综述中,我们讨论基于单克隆抗体的癌症治疗策略。我们比较天然抗体、片段化抗体、重组抗体、嵌合抗体、双特异性抗体、免疫缀合物和免疫脂质体。讨论了它们的开发原理、优势以及体外和体内性能,还有它们的临床应用价值。