隨著生物醫(yī)藥技術的不斷發(fā)展，雙特異性抗體（ BsAb）成為新藥研發(fā)的熱點。相比于傳統(tǒng)的小分子和單抗類藥物，BsAb的結構經過特殊設計，能強有力地激活免疫系統(tǒng)，但在消退腫瘤的同時也給安全性帶來了特殊風險。首先從靶點選擇和動物模型、免疫原性、非臨床藥動學等方面概述抗腫瘤BsAb非臨床安全性研究的考慮要點。其次重點關注抗腫瘤BsAb非臨床研究中常用的實驗系統(tǒng)如嚙齒類動物、非人靈長類動物和體外替代模型的優(yōu)缺點，并進行深入的討論。最后，結合已獲得美國食品藥品監(jiān)督管理局（ FDA）批準上市的11種抗腫瘤BsAb（如Catumaxomab、Blinatumomab、Amivantamab等）非臨床安全性評價實例，重點關注其實驗系統(tǒng)和安全性評價指標，探索BsAb的非臨床安全性評價策略，以期為我國抗腫瘤BsAb的研發(fā)提供參考。

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