抗體偶聯(lián)藥物、雙特異性抗體等新型抗體已成為近年來(lái)抗體工程領(lǐng)域的研究熱點(diǎn)，由于其具有特異性高、選擇性強(qiáng)和非細(xì)胞毒性等優(yōu)點(diǎn)，在腫瘤治療領(lǐng)域中具有廣闊的應(yīng)用前景。但該類藥物結(jié)構(gòu)和功能相對(duì)復(fù)雜，給安全性帶來(lái)特殊風(fēng)險(xiǎn)。在臨床前安全性評(píng)價(jià)中，需要根據(jù)其特點(diǎn)和可能介導(dǎo)的毒性作用機(jī)制，建立科學(xué)的評(píng)價(jià)方案。通過(guò)對(duì)新型抗體類藥物的類型、結(jié)構(gòu)特點(diǎn)、作用方式以及主要的毒性風(fēng)險(xiǎn)進(jìn)行綜述，并結(jié)合已批準(zhǔn)的新型抗體類藥物的非臨床安全性評(píng)價(jià)實(shí)例，探索新型抗體類藥物的臨床前安全性評(píng)價(jià)策略。

Antibody drug conjugates (ADCs) and Bispecific Antibodies are emerging as the promising class of new biopharmaceutical which have become a research focus in antibody engineering. Due to its specificity and less adverse effect,these new antibody drugs have a wide application future in cancer immunotherapy. From the nonclinical safety perspective, ADCs and Bispecific Antibodies present unique challenges to standard toxicology testing due to the complex components and mechanism of action. The impact of these biochemical differences on the safety must be considered when determining the types of nonclinical safety studies. The aim of this article is to review the unique characteristic, mode of action, determinants of toxicity, and preclinical studies of ADCs and Bispecific Antibodies to discuss how recent advances in our understanding of drug-mediated toxicity can be used to guide the types of preclinical safety studies.

十二五國(guó)家科技重大專項(xiàng)“生物大分子藥物特殊評(píng)價(jià)關(guān)鍵技術(shù)研究”（2015ZX09501007-004）；中國(guó)食品藥品檢定研究院中青年發(fā)展研究基金（2014C5）