Antibody–drug conjugates (ADC) represent one of the most rapidly expanding treatment modalities in oncology, with 11 ADCs approved by the FDA and more than 210 currently being tested in clinical trials. Spanning over 40 years, ADC clinical development has enhanced our understanding of the multifaceted mechanisms of action for this class of therapeutics. In this article, we discuss key insights into the toxicity, efficacy, stability, distribution, and fate of ADCs. Furthermore, we highlight ongoing challenges related to their clinical optimization, the development of rational sequencing strategies, and the identification of predictive biomarkers. Significance: The development and utilization of ADCs have allowed for relevant improvements in the prognosis of multiple cancer types. Concomitantly, the rise of ADCs in oncology has produced several challenges, including the prediction of their activity, their utilization in sequence, and minimization of their side effects, that still too often resemble those of the cytotoxic molecule that they carry. In this review, we retrace 40 years of development in the field of ADCs and delve deep into the mechanisms of action of these complex therapeutics and reasons behind the many achievements and failures observed in the field to date.

中文翻译：

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抗体-药物偶联物的旅程：40 年发展的经验教训


抗体-药物偶联物 （ADC） 是肿瘤学领域发展最快的治疗方式之一，FDA 批准了 11 种 ADC，目前正在临床试验中测试超过 210 种。跨越 40 多年，ADC 临床开发增强了我们对此类疗法的多方面作用机制的理解。在本文中，我们讨论了对 ADC 的毒性、疗效、稳定性、分布和命运的关键见解。此外，我们强调了与他们的临床优化、合理测序策略的开发以及预测生物标志物的识别相关的持续挑战。意义： ADC 的开发和利用使多种癌症类型的预后得到相关改善。与此同时，ADC 在肿瘤学中的兴起也带来了一些挑战，包括预测它们的活性、按顺序利用以及最小化它们的副作用，这些挑战仍然经常类似于它们携带的细胞毒性分子。在这篇综述中，我们回顾了 ADC 领域 40 年的发展，并深入研究了这些复杂疗法的作用机制以及迄今为止在该领域观察到的许多成就和失败背后的原因。