用于乳腺癌的下一代抗体药物偶联物：超越 HER2 和 TROP2。
Next-generation antibody-drug conjugates for breast cancer: Moving beyond HER2 and TROP2.
机构信息
Department of Hematology and Oncology, Tufts Medical Center, Boston, MA, USA.
Department of Internal Medicine, Brigham and Women's Hospital, Boston, MA, USA.
出版信息
Crit Rev Oncol Hematol. 2023 Oct;190:104090. doi: 10.1016/j.critrevonc.2023.104090. Epub 2023 Aug 9.
Antibody-drug conjugates (ADCs) have reshaped the treatment of several malignancies, including breast cancer. Two ADCs are currently approved for the treatment of each breast cancer subtype, including the HER2 targeted ADCs trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd), and the TROP2-targeted ADC sacituzumab govitecan. Each of the ADC components (antibody, linker, and payload) plays a key role in determining the efficacy and toxicity profile of an individual ADC, and their modification can lead to major changes in the clinical profile of these agents. Leveraging the knowledge from three decades of development in the field, several novel ADCs are currently being investigated. Some approaches include targeting different antigens beyond the established HER2/TROP2, or evaluating innovative constructs, such as bispecific ADCs, ADCs with dual payload, immune-modulating ADCs, radionuclide drug conjugates, and masked ADCs, among others. In this review article we discuss the evolving landscape of novel ADCs, highlighting opportunities and challenges emerging in the field.
抗体药物偶联物 (ADC) 改变了多种恶性肿瘤的治疗方式，包括乳腺癌。目前有两种 ADC 获批用于治疗每种乳腺癌亚型，包括针对 HER2 的 ADC 曲妥珠单抗艾米替森 (T-DM1) 和曲妥珠单抗德曲妥珠单抗 (T-DXd)，以及针对 TROP2 的 ADC Sacituzumab govitecan。每个 ADC 成分（抗体、连接子和有效载荷）在确定单个 ADC 的疗效和毒性特征方面都起着关键作用，对它们的修饰可能会导致这些药物的临床特征发生重大变化。利用该领域三十年来的发展知识，目前正在研究几种新型 ADC。一些方法包括针对除已确立的 HER2/TROP2 以外的不同抗原，或评估创新的结构，如双特异性 ADC、具有双重有效载荷的 ADC、免疫调节 ADC、放射性药物偶联物和掩蔽 ADC 等。在这篇综述文章中，我们讨论了新型 ADC 的不断发展的前景，强调了该领域出现的机遇和挑战。
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