Chen Hao, Lin Zongtao, Arnst Kinsie E, Miller Duane D, Li Wei
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Avenue, Room 561, Memphis, TN 38163, USA.
Molecules. 2017 Aug 1;22(8):1281. doi: 10.3390/molecules22081281.
Antibody-drug conjugates (ADCs) are a class of highly potent biopharmaceutical drugs generated by conjugating cytotoxic drugs with specific monoclonal antibodies through appropriate linkers. Specific antibodies used to guide potent warheads to tumor tissues can effectively reduce undesired side effects of the cytotoxic drugs. An in-depth understanding of antibodies, linkers, conjugation strategies, cytotoxic drugs, and their molecular targets has led to the successful development of several approved ADCs. These ADCs are powerful therapeutics for cancer treatment, enabling wider therapeutic windows, improved pharmacokinetic/pharmacodynamic properties, and enhanced efficacy. Since tubulin inhibitors are one of the most successful cytotoxic drugs in the ADC armamentarium, this review focuses on the progress in tubulin inhibitor-based ADCs, as well as lessons learned from the unsuccessful ADCs containing tubulin inhibitors. This review should be helpful to facilitate future development of new generations of tubulin inhibitor-based ADCs for cancer therapy.
抗体药物偶联物（ADCs）是一类高效的生物制药，通过合适的连接子将细胞毒性药物与特异性单克隆抗体偶联而成。用于将强效弹头导向肿瘤组织的特异性抗体可有效减少细胞毒性药物的不良副作用。对抗体、连接子、偶联策略、细胞毒性药物及其分子靶点的深入了解促成了几种已获批ADC的成功研发。这些ADC是癌症治疗的有力疗法，具有更宽的治疗窗口、改善的药代动力学/药效学特性以及更高的疗效。由于微管蛋白抑制剂是ADC药物库中最成功的细胞毒性药物之一，本综述重点关注基于微管蛋白抑制剂的ADC的进展，以及从含微管蛋白抑制剂的未成功ADC中吸取的教训。本综述应有助于推动新一代基于微管蛋白抑制剂的ADC用于癌症治疗的未来发展。
