随着生物医药技术的不断发展，双特异性抗体（ BsAb）成为新药研发的热点。相比于传统的小分子和单抗类药物，BsAb的结构经过特殊设计，能强有力地激活免疫系统，但在消退肿瘤的同时也给安全性带来了特殊风险。首先从靶点选择和动物模型、免疫原性、非临床药动学等方面概述抗肿瘤BsAb非临床安全性研究的考虑要点。其次重点关注抗肿瘤BsAb非临床研究中常用的实验系统如啮齿类动物、非人灵长类动物和体外替代模型的优缺点，并进行深入的讨论。最后，结合已获得美国食品药品监督管理局（ FDA）批准上市的11种抗肿瘤BsAb（如Catumaxomab、Blinatumomab、Amivantamab等）非临床安全性评价实例，重点关注其实验系统和安全性评价指标，探索BsAb的非临床安全性评价策略，以期为我国抗肿瘤BsAb的研发提供参考。

In recent years, bispecific antibodies (BsAb) have been the spotlights of new therapeutics development, with the dramatic expansion of the biotechnology. Comparing to the traditional small molecules and monoclonal antibodies, BsAb are structurally engineered to potently activate the immune system, offering robust tumor regression while exiting unique safety risks. This paper initially outlines key considerations for nonclinical safety studies of anti-tumor BsAb, encompassing target selection, animal models, immunogenicity, and nonclinical pharmacokinetics. Then given the pivotal role of experimental systems in nonclinical research, we discussed the advantages and disadvantages of commonly utilized experimental systems in anti-tumor BsAb nonclinical studies, such as rodents, non-human primates, and in vitro alternative models. Finally, combining the examples of non-clinical safety evaluation of 11 anti-tumor BsAb such as Catumaxomab, Blinatumomab and Amivantamab which have been approved by the US FDA, and focusing on their experimental systems and safety evaluation parameters, explored the strategy of non-clinical safety evaluation of BsAb with the aim of providing the research and development of antitumor BsAb in China.

R979.1