Introduced almost two decades ago, ADCs have marked a breakthrough in the targeted therapy era, providing clinical benefits to many cancer patients. While the inherent complexity of this class of drugs has challenged their development and broad application, the experience gained from years of trials and errors and recent advances in construct design and delivery have led to an increased number of ADCs approved or in late clinical development in only five years. Target and payload diversification, along with novel conjugation and linker technologies, are at the forefront of next-generation ADC development, renewing hopes to broaden the scope of these targeted drugs to difficult-to-treat cancers and beyond. This review highlights recent trends in the ADC field, focusing on construct design and mechanism of action and their implications on ADCs’ therapeutic profile. The evolution from conventional to innovative ADC formats will be illustrated, along with some of the current hurdles, including toxicity and drug resistance. Future directions to improve the design of next-generation ADCs will also be presented.
抗体偶联药物（ADC）问世近二十年来，已成为靶向治疗时代的重大突破，为众多癌症患者带来临床获益。尽管这类药物固有的复杂性给其研发与广泛应用带来挑战，但通过多年试错积累的经验，以及近年来在结构设计与递送技术方面的进步，使得过去五年间获批或进入临床后期研发阶段的ADC数量显著增加。靶点与载荷的多样化，结合新型偶联与连接子技术，正引领下一代ADC研发的前沿，为拓展这类靶向药物治疗难治性癌症及其他疾病的范畴注入新希望。本综述聚焦ADC领域最新趋势，重点探讨结构设计、作用机制及其对ADC治疗特性的影响，阐述从传统到创新型ADC的演进历程，并剖析当前面临的毒性及耐药性等挑战，同时展望优化下一代ADC设计的未来方向。
Antibody–Drug Conjugates: The Dynamic Evolution from Conventional to Next-Generation Constructs
肿瘤(癌症)患者之家