Manabe Shino
Hoshi University, Laboratory of Synthetic Biomolecular Chemistry.
Gan To Kagaku Ryoho. 2024 Jul;51(7):681-685.
The efficacy of antibody-drug conjugates(ADCs)has been well-established in clinical use, prompting ongoing research and development efforts to advance the field of ADCs further. This chapter provides overview of the structure and mechanism of action of ADCs, detailing the roles of its components: the antibody, the payload, and the linker. ADCs leak from cancer vessels to bind to specific antigens on the surface of tumor cells. Upon binding and internalization, the drug is released by metabolic enzymes, such as peptidases in the lysosome. The therapeutic window of the conjugated drug is therefore expanded. To enhance the efficacy of ADCs, the chapter will also explore the development of methodologies for generating homogeneous ADCs and the concept of bystander effects, which are particularly relevant in the tumor microenvironment. Additionally, innovative approaches such as radioimmunotherapy, utilizing alpha-ray emitting radionuclides, and photoimmunotherapy, are discussed as promising next-generation ADC strategies. The integration of ADCs with immunotherapy may offer amplified effectiveness through synergistic actions. The chapter underscores that the prolonged therapeutic impact of ADCs cannot be solely attributed to the targeted delivery and controlled release of the payload. A comprehensive understanding from the perspective of cancer immunology is imperative for elucidating the underlying mechanisms contributing to their sustained efficacy.
抗体药物偶联物（ADCs）在临床应用中的疗效已得到充分证实，这促使人们不断进行研发工作，以进一步推动ADC领域的发展。本章概述了ADCs的结构和作用机制，详细介绍了其组成部分的作用：抗体、有效载荷和连接子。ADCs从癌血管渗漏出来，与肿瘤细胞表面的特定抗原结合。结合并内化后，药物由代谢酶（如溶酶体中的肽酶）释放出来。因此，偶联药物的治疗窗口得以扩大。为了提高ADCs的疗效，本章还将探讨生成均一ADCs的方法的发展以及旁观者效应的概念，这在肿瘤微环境中尤为相关。此外，还讨论了诸如利用发射α射线的放射性核素的放射免疫疗法和光免疫疗法等创新方法，作为有前景的下一代ADC策略。将ADCs与免疫疗法相结合可能通过协同作用提供增强的疗效。本章强调，ADCs的长期治疗效果不能仅仅归因于有效载荷的靶向递送和控释。从癌症免疫学的角度进行全面理解对于阐明其持续疗效的潜在机制至关重要。
