Chen Miaomiao, Zhou Yuli, Bao Kaicheng, Chen Siyu, Song Guoqing, Wang Siliang
Department of Oncology, Shengjing Hospital of China Medical University, 36 Sanhao Road, Shenyang, 110004, China.
Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China.
BioDrugs. 2025 May;39(3):427-444. doi: 10.1007/s40259-025-00712-6. Epub 2025 Mar 19.
The development of immune checkpoint inhibitors has revolutionized the treatment of patients with cancer. Targeting the programmed cell death protein 1 (PD-1)/programmed cell death 1 ligand 1(PD-L1) interaction using monoclonal antibodies has emerged as a prominent focus in tumor therapy with rapid advancements. However, the efficacy of anti-PD-1/PD-L1 treatment is hindered by primary or acquired resistance, limiting the effectiveness of single-drug approaches. Moreover, combining PD-1/PD-L1 with other immune drugs, targeted therapies, or chemotherapy significantly enhances response rates while exacerbating adverse reactions. Multispecific antibodies, capable of binding to different epitopes, offer improved antitumor efficacy while reducing drug-related side effects, serving as a promising therapeutic approach in cancer treatment. Several bispecific antibodies (bsAbs) targeting PD-1/PD-L1 have received regulatory approval, and many more are currently in clinical development. Additionally, tri-specific antibodies (TsAbs) and tetra-specific antibodies (TetraMabs) are under development. This review comprehensively explores the fundamental structure, preclinical principles, clinical trial progress, and challenges associated with bsAbs targeting PD-1/PD-L1.
免疫检查点抑制剂的发展彻底改变了癌症患者的治疗方式。使用单克隆抗体靶向程序性细胞死亡蛋白1（PD-1）/程序性细胞死亡1配体1（PD-L1）相互作用已成为肿瘤治疗的一个突出重点，并取得了快速进展。然而，抗PD-1/PD-L1治疗的疗效受到原发性或获得性耐药的阻碍，限制了单药治疗方法的有效性。此外，将PD-1/PD-L1与其他免疫药物、靶向疗法或化疗联合使用可显著提高缓解率，但同时会加剧不良反应。能够结合不同表位的多特异性抗体在提高抗肿瘤疗效的同时减少了药物相关副作用，是癌症治疗中一种有前景的治疗方法。几种靶向PD-1/PD-LI的双特异性抗体（bsAbs）已获得监管批准，目前还有更多处于临床开发阶段。此外，三特异性抗体（TsAbs）和四特异性抗体（四价抗体）也在研发中。本综述全面探讨了靶向PD-1/PD-L1的双特异性抗体的基本结构、临床前原理、临床试验进展及相关挑战。
