Anticancer carrier-linked prodrugs in clinical trials

被引:75
作者
Kratz, Felix [1 ]
Abu Ajaj, Khalid [1 ]
Warnecke, Andre [1 ]
机构
[1] Tumor Biol Ctr, Macromol Prodrugs, D-79106 Freiburg, Germany
关键词
antibodies; anticancer prodrugs; cancer chemotherapy; drug targeting; polymer therapeutics;
D O I
10.1517/13543784.16.7.1037
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Coupling of low molecular weight anticancer drugs to antibodies, serum proteins or polymers through a cleavable linker has been an effective method for improving the therapeutic index of cytotoxic established agents. Modern drug-antibody conjugates that have recently entered clinical trials have primarily used highly potent drugs such as calicheamicin or maytansins. Gemtuzumab ozogamicin, a conjugate of calicheamicin and an anti-CD33 humanized antibody, is the first drug-antibody conjugate to receive market approval. Drug conjugates that have undergone clinical assessment include N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates with doxorubicin, camptothecin, paclitaxel and Pt(II) complexes, poly(ethylene glycol) conjugates with camptothecin and paclitaxel, polyglutamate conjugates with paclitaxel and camptothecin, a methotrexate-albumin conjugate and an albumin-binding doxorubicin prodrug. This review summarizes the Phase I - III studies that have been performed with these macromolecular prodrugs.
引用
收藏
页码:1037 / 1058
页数:22
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