Department of Life Science, Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea.
Exp Mol Med. 2011 Oct 31;43(10):539-49. doi: 10.3858/emm.2011.43.10.063.
To date, more than 30 antibodies have been approved worldwide for therapeutic use. While the monoclonal antibody market is rapidly growing, the clinical use of therapeutic antibodies is mostly limited to treatment of cancers and immunological disorders. Moreover, antibodies against only five targets (TNF-α, HER2, CD20, EGFR, and VEGF) account for more than 80 percent of the worldwide market of therapeutic antibodies. The shortage of novel, clinically proven targets has resulted in the development of many distinct therapeutic antibodies against a small number of proven targets, based on the premise that different antibody molecules against the same target antigen have distinct biological and clinical effects from one another. For example, four antibodies against TNF-α have been approved by the FDA -- infliximab, adalimumab, golimumab, and certolizumab pegol -- with many more in clinical and preclinical development. The situation is similar for HER2, CD20, EGFR, and VEGF, each having one or more approved antibodies and many more under development. This review discusses the different binding characteristics, mechanisms of action, and biological and clinical activities of multiple monoclonal antibodies against TNF-α, HER-2, CD20, and EGFR and provides insights into the development of therapeutic antibodies.
迄今为止，全球已有 30 多种抗体获批用于治疗用途。虽然单克隆抗体市场正在迅速增长，但治疗性抗体的临床应用主要限于癌症和免疫性疾病的治疗。此外，针对仅 5 个靶点（TNF-α、HER2、CD20、EGFR 和 VEGF）的抗体占治疗性抗体全球市场的 80%以上。由于缺乏新的、经过临床验证的靶点，因此针对少数已证实的靶点开发了许多不同的治疗性抗体，其前提是针对同一靶抗原的不同抗体分子彼此之间具有不同的生物学和临床效应。例如，已有四种针对 TNF-α 的抗体获得 FDA 批准——英夫利昔单抗、阿达木单抗、戈利木单抗和certolizumab pegol——还有更多的抗体正在临床和临床前开发中。HER2、CD20 和 EGFR 也是如此，每种都有一个或多个已批准的抗体，还有更多的在开发中。本文综述了针对 TNF-α、HER-2、CD20 和 EGFR 的多种单克隆抗体的不同结合特性、作用机制以及生物学和临床活性，并深入探讨了治疗性抗体的开发。
