派安普利单抗：一种用于癌症免疫治疗的下一代Fc工程化PD-1抑制剂。

文献信息

中文摘要

派安普利单抗（AK105）是一种新型Fc工程化、人源化IgG₁单克隆抗体，靶向程序性细胞死亡蛋白-1（PD-1）。与传统PD-1抑制剂不同，派安普利单抗被设计为消除Fcγ受体和补体C1q结合，从而减少Fc介导的效应功能，同时保持抗肿瘤免疫活性。临床前研究已证明其结构稳定性增强、受体占据时间延长以及对PD-1的高亲和力结合。在血液系统和实体恶性肿瘤（包括经典霍奇金淋巴瘤、鼻咽癌、非小细胞肺癌和肝细胞癌）中的临床研究已显示出有希望的疗效，表现为持久缓解和改善的无进展生存期。派安普利单抗与化疗和靶向治疗联合使用时也表现出良好的结局。安全性特征总体可控，最常见的报告不良事件为甲状腺功能减退、疲劳、皮疹、发热和胃肠道毒性。新出现的证据表明，Fc工程化可能有助于减少免疫相关毒性。总体而言，派安普利单抗提供了一种有前景的下一代PD-1抑制剂，在多种恶性肿瘤中具有潜在应用价值。

英文摘要

Penpulimab (AK105) is a novel Fc-engineered, humanised IgG₁ monoclonal antibody targeting programmed cell death protein-1 (PD-1). Unlike conventional PD-1 inhibitors, penpulimab has been designed to eliminate Fcγ receptor and complement C1q binding, thereby reducing Fc-mediated effector functions while maintaining antitumour immune activity. Preclinical studies have demonstrated enhanced structural stability, prolonged receptor occupancy, and high-affinity binding to PD-1. Clinical investigations across haematological and solid malignancies, including classical Hodgkin lymphoma, nasopharyngeal carcinoma, non-small-cell lung cancer, and hepatocellular carcinoma, have shown promising efficacy with durable responses and improved progression-free survival. Penpulimab has also demonstrated favourable outcomes when combined with chemotherapy and targeted therapies. The safety profile is generally manageable, with hypothyroidism, fatigue, rash, pyrexia, and gastrointestinal toxicities being the most commonly reported adverse events. Emerging evidence suggests that Fc engineering may contribute to reduced immune-related toxicity. Overall, penpulimab offers a promising next-generation PD-1 inhibitor with potential applications across multiple malignancies.