抗體偶聯(lián)藥物（ADC）是由抗體、有效載荷（細(xì)胞毒性小分子化合物）和連接子組成的新型特異性抗腫瘤藥物。ADC具有高特異性和不良反應(yīng)少等特點，但其安全性受到抗體特異性、連接子穩(wěn)定性和有效載荷性質(zhì)等因素的影響。ADC的劑量限制性毒性主要與有效載荷有關(guān)，且在臨床和非臨床研究中具有很好的相關(guān)性。ADC的毒性機(jī)制包括靶向毒性和脫靶毒性，靶向毒性主要由靶點的表達(dá)決定，脫靶毒性則由偶聯(lián)不穩(wěn)定和非特異性攝取等因素引起。簡要概述ADC的毒性機(jī)制，重點介紹ADC非臨床安全性評價中的毒性病理學(xué)檢查關(guān)注點，以期為我國ADC非臨床安全性評價提供一定參考。

Antibody-drug conjugate drug (ADC) are novel specific anti-tumor drugs composed of antibodies, payloads (cytotoxic small molecule compounds) and linkers. ADC is characterized by high specificity and few side effects, but their safety is affected by factors such as antibody specificity, stability of linker, and nature of payload. The dose-limiting toxicity of ADC is mainly related to the payload and has been well correlated in clinical and nonclinical studies. The toxicity mechanism of ADC includes on-target toxicity and off-target toxicity. On-target toxicity is mainly determined by the expression of the target, whereas off-target toxicity is caused by factors such as coupling instability and non-specific uptake. The toxicity mechanism of ADC is briefly reviewed, and the toxicologic pathology examination during nonclinical safety evaluation of ADC is emphasized, so as to provide some references for the nonclinical safety evaluation of ADC in China.

R965.1

基于AI的創(chuàng)新藥物研發(fā)服務(wù)平臺項目