结合
体内
抗体
连接器
化学
抗体-药物偶联物
内化
癌症研究
药品
药理学
医学
单克隆抗体
免疫学
生物化学
生物
计算机科学
生物技术
细胞
数学分析
操作系统
数学
作者
Alberto Dal Corso,Rémy Gébleux,Patrizia Murer,Alex Soltermann,Dario Neri
标识
DOI:10.1016/j.jconrel.2017.08.040
摘要
Antibody-drug conjugates are generally believed to crucially rely on internalization into cancer cells for therapeutic activity. Here, we show that a non-internalizing antibody-drug conjugate, based on the F16 antibody specific to the alternatively spliced A1 domain of tenascin-C, mediates a potent therapeutic activity when equipped with the anthracycline PNU159682. The peptide linker, connecting the F16 antibody in IgG format at a specific cysteine residue to the drug, was stable in serum but could be efficiently cleaved in the subendothelial extracellular matrix by proteases released by the dying tumor cells. The results indicate that there may be a broader potential applicability of non-internalizing antibody-drug conjugates for cancer therapy than what had previously been assumed.
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