Helsinki University Hospital and University of Helsinki Helsinki Finland.
Laboratory of Molecular Oncology University of Helsinki Biomedicum Helsinki Finland.
J Extracell Vesicles. 2021 Feb;10(4):e12070. doi: 10.1002/jev2.12070. Epub 2021 Feb 13.
Antibody-drug conjugates (ADCs) are a new class of anti-cancer drugs that consist of a monoclonal antibody, a highly potent small-molecule cytotoxic drug, and a chemical linker between the two. ADCs can selectively deliver cytotoxic drugs to cancer cells leading to a reduced systemic exposure and a wider therapeutic window. To date, nine ADCs have received marketing approval, and over 100 are being investigated in nearly 600 clinical trials. The target antigens of at least eight out of the nine approved anti-cancer ADCs and of 69 investigational ADCs are present on extracellular vesicles (EVs) (tiny particles produced by almost all types of cells) that may carry their contents into local and distant cells. Therefore, the EVs have a potential to mediate both the anti-cancer effects and the adverse effects of ADCs. In this overview, we discuss the mechanisms of action of ADCs and the resistance mechanisms to them, the EV-mediated resistance mechanisms to small molecule anti-cancer drugs and anti-cancer monoclonal antibodies, and the EVs as modifiers of ADC efficacy and safety.
抗体偶联药物（ADCs）是一类新型的抗癌药物，由单克隆抗体、一种高效的小分子细胞毒性药物和两者之间的化学连接子组成。ADC 可以选择性地将细胞毒性药物递送到癌细胞中，从而降低全身暴露和扩大治疗窗口。迄今为止，已有 9 种 ADC 获得了市场批准，近 600 项临床试验正在研究超过 100 种 ADC。在至少 9 种已批准的抗癌 ADC 中的 8 种和 69 种研究中的 ADC 的靶抗原存在于细胞外囊泡（EVs）（几乎所有类型的细胞产生的微小颗粒）中，这些 EVs 可能将其内容物带入局部和远处的细胞。因此，EVs 有可能介导 ADC 的抗癌作用和不良反应。在这篇综述中，我们讨论了 ADC 的作用机制和对它们的耐药机制，小分子抗癌药物和抗癌单克隆抗体的 EV 介导的耐药机制，以及 EV 作为 ADC 疗效和安全性的调节剂。
