Han Lijie, Wang Ke, Jiang Zhongxing, Guo Xuejun, Yu Jifeng
Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
Department of Hematology/Oncology, Puyang Oilfield General Hospital Affiliated with Xinxiang Medical College, Puyang, China.
Crit Rev Oncol Hematol. 2025 May 2;212:104752. doi: 10.1016/j.critrevonc.2025.104752.
While monoclonal antibody (mAb)-based therapies have revolutionized cancer treatment, challenges such as resistance mechanisms and tumor progression via alternative pathways underscore the need for novel therapeutic strategies. Bispecific antibodies (BsAbs), which target two distinct antigens simultaneously, represent a promising next-generation solution, improving therapeutic precision, efficacy, and safety. BsAbs also redirect cytotoxic effector cells to tumor sites, providing additional therapeutic mechanisms. Recent advancements in BsAb design, such as enhancements in pharmacokinetics and modular multi-specific formats, are expanding their use in hematological malignancies. Combining BsAbs with immune checkpoint inhibitors and other therapies may overcome resistance and improve clinical outcomes. Leading BsAbs, including mosunetuzumab, glofitamab, and blinatumomab, have demonstrated promising efficacy in clinical trials for leukemia and lymphoma subtypes. Despite remaining challenges, particularly in acute myeloid leukemia (AML), ongoing research into new targets and combination therapies is expected to enhance the efficacy of BsAbs in relapsed or refractory (R/R) disease. This review explores the structural and functional innovations of BsAbs, the challenges in current therapies, and their transformative potential in hematological malignancy immunotherapy.
虽然基于单克隆抗体（mAb）的疗法彻底改变了癌症治疗方式，但诸如耐药机制和通过替代途径导致肿瘤进展等挑战凸显了新型治疗策略的必要性。双特异性抗体（BsAb）可同时靶向两种不同抗原，是一种很有前景的下一代解决方案，可提高治疗的精准性、疗效和安全性。BsAb还能将细胞毒性效应细胞重定向至肿瘤部位，提供额外的治疗机制。BsAb设计的最新进展，如药代动力学的改善和模块化多特异性形式，正在扩大其在血液系统恶性肿瘤中的应用。将BsAb与免疫检查点抑制剂及其他疗法联合使用可能克服耐药性并改善临床结果。包括莫苏努单抗、格洛菲他单抗和博纳吐单抗在内的领先BsAb在白血病和淋巴瘤亚型的临床试验中已显示出有前景的疗效。尽管仍存在挑战，尤其是在急性髓系白血病（AML）中，但对新靶点和联合疗法的持续研究有望提高BsAb在复发或难治性（R/R）疾病中的疗效。本综述探讨了BsAb的结构和功能创新、当前治疗中的挑战及其在血液系统恶性肿瘤免疫治疗中的变革潜力。
