体内
离体
药理学
抗体-药物偶联物
化学
抗体
癌症研究
医学
单克隆抗体
生物
免疫学
生物技术
作者
Yiquan Li,Zihao Wang,Yuchao Dong,Xiaoyang Yu,Jing Lu,Ningyi Jin,Chao Shang,Xiao Li,Shiyong Fan
出处
期刊:Biomaterials
[Elsevier]
日期:2023-10-01
卷期号:301: 122258-122258
标识
DOI:10.1016/j.biomaterials.2023.122258
摘要
Many clinical trials of kinesin spindle protein (KSP) inhibitors have failed due to issues such as high toxicity and a short circulation half-life in vivo. To address the limitations of current KSP inhibitors and thus broad its use in antitumor therapy, this study applied antibody–drug conjugate (ADC) technology to the KSP inhibitor SB-743921, which was coupled with the HER2-specific antibody trastuzumab using a cathepsin B-dependent valine–alanine (Val–Ala, VA) dipeptide-type linker to generate H2-921. Ex vivo and in vivo analyses of H2-921 showed an increased half-life of SB-743921 and prolonged contact time with tumor cells. Furthermore, H2-921 induced apoptosis and incomplete autophagy in HER2-positive cells. In the in vivo analyses, H2-921 had significant tumor-targeting properties, and tumor inhibition by H2-921 was greater than that by traditional KSP inhibitors but similar to that by the positive control drug T-DM1. In conclusion, this study describes a novel application of ADC technology that enhances the antitumor effects of a KSP inhibitor and thus may effectively address the poor clinical efficacy of KSP inhibitors.
科研通智能强力驱动
Strongly Powered by AbleSci AI