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肿瘤治疗中的三特异性抗体:机制、临床进展与未来方向

英文原题:Trispecific antibodies in cancer therapy: Mechanisms, clinical progress and future directions.

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Trispecific antibodies in cancer therapy: Mechanisms, clinical progress and future directions.

PubMed 2026/03/18(内容时间) Int Immunopharmacol Q1 · IF 5.6(JCR 2025)

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中文摘要

三特异性抗体代表了一类新兴的下一代抗体治疗药物,在肿瘤免疫治疗中的相关性日益增强。通过同时结合三个不同的靶点,这些分子被设计用于整合多种抗肿瘤机制,从而增强免疫介导的肿瘤细胞清除。尽管这一概念具有吸引力,但三特异性抗体的开发和临床转化仍处于早期阶段。本综述总结了三特异性抗体候选药物的当前临床格局,并讨论了支撑其设计近期进展的分子和机制原理。在血液系统恶性肿瘤和部分实体瘤中的早期临床经验表明,其具有令人鼓舞的抗肿瘤活性,且安全性总体可控。

然而,三特异性抗体形式固有的结构复杂性给大规模生产带来了重大挑战,导致生产成本增加。此外,药代动力学方面的局限性——包括体内稳定性、全身半衰期和组织穿透性——仍有待充分优化。免疫原性相关毒性,以及疗效与安全性之间的长期平衡,也是需要仔细临床评估的关键问题。

总体而言,三特异性抗体在拓展肿瘤免疫治疗范围方面具有相当大的前景。分子工程、生物工艺开发和临床研究方面的持续进展,对于克服现有障碍并实现其全部治疗潜力至关重要。

展开英文摘要原文

Trispecific antibodies represent an emerging class of next-generation antibody therapeutics, with growing relevance in cancer immunotherapy. By simultaneously engaging three distinct targets, these molecules are designed to integrate multiple antitumor mechanisms, thereby augmenting immune-mediated tumor cell elimination. Despite this conceptual appeal, the development and clinical translation of trispecific antibodies remain at an early stage.

This review summarizes the current clinical landscape of trispecific antibody candidates and discusses the molecular and mechanistic principles underpinning recent advances in their design. Early clinical experience in hematological malignancies and selected solid tumors indicates encouraging antitumor activity with generally manageable safety profiles.

However, the intrinsic structural complexity of trispecific antibody formats poses substantial challenges for large-scale manufacturing, contributing to increased production costs.

In addition, pharmacokinetic limitations-including in vivo stability, systemic half-life, and tissue penetration-remain to be fully optimized. Immunogenicity-related toxicities, together with the long-term balance between efficacy and safety, also represent critical issues that necessitate careful clinical evaluation.

Overall, trispecific antibodies hold considerable promise for expanding the therapeutic scope of cancer immunotherapy. Continued advances in molecular engineering, bioprocess development, and clinical investigation will be essential to overcome existing barriers and to realize their full therapeutic potential.

论文信息

作者
Liu X、Fan X、Wang Y、Wang L、Lu D、Wang Y、Meng X、Fan L
第一作者单位
Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China; Qingdao Cancer Institute, Qingdao, China; School of Basic Medicine, Qingdao Medical College, Qingdao University, Qingdao, China.China
通讯作者单位
Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China. Electronic address: psun1@qdu.edu.cn.China
文献类型
综述
期刊
International immunopharmacology2026 May 15
原文标识
PubMed 41855774 · DOI 10.1016/j.intimp.2026.116503