Xu Xiaoxiao, Yu Tong, Wang Zhenxing
Department of Breast Cancer, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang 110042, PR China.
Department of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical University, Shenyang 110042, PR China.
Cancer Treat Rev. 2025 Aug 11;140:103012. doi: 10.1016/j.ctrv.2025.103012.
The use of antibody-drug conjugates (ADCs) and immune checkpoint inhibitors (ICIs) has revolutionized the treatment of breast cancer. ADCs deliver cytotoxic payloads to tumor cells via antigen-targeted monoclonal antibodies, triggering direct cytotoxicity and immunomodulatory effects such as immunogenic cell death (ICD), antibody-dependent cellular cytotoxicity (ADCC), and dendritic cell activation. Preclinical and clinical studies highlight the synergistic effect of combining ADCs with ICIs: ADCs enhance tumor immunogenicity by releasing neoantigens, while ICIs reinvigorate T-cell-mediated antitumor responses by blocking the PD-1/PD-L1 or CTLA-4 pathways. This review explores the synergistic potential of combining ADCs and ICIs in the treatment of breast cancer, with an emphasis on mechanistic synergy and clinical outcomes. Notably, overlapping toxicities require careful monitoring. Additionally, novel immune checkpoint-targeted drug conjugates (IDCs) exhibit potential through dual-targeting and immunomodulatory mechanisms. Future efforts should focus on optimizing patient selection and developing next-generation conjugates to maximize efficacy while minimizing adverse effects.
抗体药物偶联物（ADCs）和免疫检查点抑制剂（ICIs）的应用彻底改变了乳腺癌的治疗方式。ADCs通过抗原靶向单克隆抗体将细胞毒性药物传递至肿瘤细胞，引发直接细胞毒性和免疫调节效应，如免疫原性细胞死亡（ICD）、抗体依赖性细胞毒性（ADCC）以及树突状细胞活化。临床前和临床研究突出了将ADCs与ICIs联合使用的协同效应：ADCs通过释放新抗原增强肿瘤免疫原性，而ICIs通过阻断PD-1/PD-L1或CTLA-4通路重振T细胞介导的抗肿瘤反应。本综述探讨了在乳腺癌治疗中联合使用ADCs和ICIs的协同潜力，重点关注机制协同作用和临床结果。值得注意的是，重叠毒性需要仔细监测。此外，新型免疫检查点靶向药物偶联物（IDCs）通过双靶点和免疫调节机制展现出潜力。未来的工作应聚焦于优化患者选择以及开发下一代偶联物，以在将不良反应降至最低的同时最大化疗效。
