Department of Hematology, Shandong Provincial Hospital, Shandong University, Jinan.
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University.
Curr Opin Oncol. 2024 Sep 1;36(5):430-436. doi: 10.1097/CCO.0000000000001065. Epub 2024 Jun 28.
Antibody-drug conjugates (ADCs), consisting of monoclonal antibodies (mAbs) covalently linked to cytotoxic drugs via chemical linkers, are a kind of promising tumor immunotherapy. ADCs also face a number of challenges, including unavoidable adverse effects, drug resistance, tumor targeting and payload release. To address these issues, in addition to optimizing the individual components of ADCs, such as new payloads, linkage sites and new targets, and using bispecific antibodies to increase precision, attention should be paid to optimizing the dosage of ADCs.
There are currently 7 ADCs approved for marketing by the Food and Drug Administration (FDA) for hematological malignancies, and dozens of other ADCs are either in clinical trials or in the process of applying for marketing. In recent clinical studies targeting ADCs in hematologic malignancies, in addition to validating effectiveness in different indications, researchers have attempted to combine ADCs with other chemotherapeutic agents in anticipation of increased therapeutic efficacy. Furthermore, the availability of bispecific antibodies may increase the safety and efficacy of ADCs.
This review summarized the progress of research on ADCs in hematological malignancies, the challenges being faced, and possible future directions to improve the efficacy of ADCs, which can provide novel insight into the future exploration of ADCs in the treatment of hematological malignancies.
抗体药物偶联物（ADC）由单克隆抗体（mAb）通过化学连接子与细胞毒性药物共价连接而成，是一种很有前途的肿瘤免疫疗法。ADC 还面临许多挑战，包括不可避免的不良反应、耐药性、肿瘤靶向和有效载荷释放。为了解决这些问题，除了优化 ADC 的各个组成部分（如新的有效载荷、连接点和新的靶点）以及使用双特异性抗体来提高精度外，还应注意优化 ADC 的剂量。
目前有 7 种 ADC 被美国食品和药物管理局（FDA）批准用于治疗血液系统恶性肿瘤，还有几十种 ADC 正在临床试验或申请上市。在最近针对血液系统恶性肿瘤 ADC 的临床研究中，除了在不同适应证中验证疗效外，研究人员还尝试将 ADC 与其他化疗药物联合使用，以期提高治疗效果。此外，双特异性抗体的出现可能会提高 ADC 的安全性和疗效。
本文综述了血液系统恶性肿瘤中 ADC 的研究进展、面临的挑战以及可能的未来方向，以提高 ADC 的疗效，为今后探索 ADC 治疗血液系统恶性肿瘤提供了新的思路。
