Antibody–drug conjugates (ADCs) combine the specificity of monoclonal antibodies with the potency of highly cytotoxic agents, potentially reducing the severity of side effects by preferentially targeting their payload to the tumour site. ADCs are being increasingly used in combination with other agents, including as first-line cancer therapies. As the technology to produce these complex therapeutics has matured, many more ADCs have been approved or are in late-phase clinical trials. The diversification of antigenic targets as well as bioactive payloads is rapidly broadening the scope of tumour indications for ADCs. Moreover, novel vector protein formats as well as warheads targeting the tumour microenvironment are expected to improve the intratumour distribution or activation of ADCs, and consequently their anticancer activity for difficult-to-treat tumour types. However, toxicity remains a key issue in the development of these agents, and better understanding and management of ADC-related toxicities will be essential for further optimization. This Review provides a broad overview of the recent advances and challenges in ADC development for cancer treatment.

抗体-药物偶联物 (ADC) 将单克隆抗体的特异性与高细胞毒性药物的效力相结合，通过优先将其有效负载靶向肿瘤部位，有可能降低副作用的严重程度。ADC 越来越多地与其他药物联合使用，包括作为一线癌症疗法。随着生产这些复杂疗法的技术已经成熟，更多的 ADC 已获得批准或正在进行后期临床试验。抗原靶点和生物活性有效负载的多样化正在迅速扩大 ADC 的肿瘤适应症范围。此外，新型载体蛋白形式以及针对肿瘤微环境的弹头有望改善 ADC 的肿瘤内分布或激活，从而改善其对难以治疗的肿瘤类型的抗癌活性。然而，毒性仍然是这些药物开发中的一个关键问题，更好地理解和管理 ADC 相关的毒性对于进一步优化至关重要。本综述全面概述了癌症治疗 ADC 开发的最新进展和挑战。