In vivo characterization of horseradish peroxidase with indole-3-acetic acid and 5-bromoindole-3-acetic acid for gene therapy of cancer

被引：0
作者：
J Tupper
M R Stratford
S Hill
G M Tozer
G U Dachs
机构：
[1] Gray Cancer Institute,
[2] Mount Vernon Hospital,undefined
[3] 2Current address: Gray Institute for Radiation Oncology and Biology,undefined
[4] University of Oxford,undefined
[5] Old Road Campus Research Building,undefined
[6] Oxford OX3 7DQ,undefined
[7] UK.,undefined
[8] 3Current address: Gray Institute for Radiation Oncology and Biology,undefined
[9] Radiobiology Research Institute,undefined
[10] University of Oxford,undefined
[11] Churchill Hospital,undefined
[12] Oxford OX3 7LJ,undefined
[13] UK.,undefined
[14] 4Current address: Tumour Microcirculation Group,undefined
[15] University of Sheffield,undefined
[16] School of Medicine and Biomedical Sciences,undefined
[17] Beech Hill Road,undefined
[18] Sheffield S10 2RX,undefined
[19] UK.,undefined
[20] 5Current address: Angiogenesis and Cancer Research Group,undefined
[21] University of Otago,undefined
[22] Christchurch,undefined
[23] New Zealand.,undefined
来源：
Cancer Gene Therapy | 2010年 / 17卷
关键词：
HRP; indoles; IAA; 5Br-IAA; xenograft; mouse model;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Gene-directed enzyme prodrug therapy is a form of targeted cancer therapy, in which an enzyme is used to convert a non-toxic prodrug to a cytotoxin within the tumor. Horseradish peroxidase (HRP) is able to convert the indole prodrugs indole-3-acetic acid (IAA) and the halogenated derivative 5-bromo-IAA (5Br-IAA) to toxic agents able to induce cell kill in vitro. This study characterized HRP-directed gene therapy in vivo. Human nasopharyngeal squamous cell carcinoma cells, FaDu, stably expressing HRP were grown as xenografts in SCID mice. Pharmacokinetic analysis of IAA and 5Br-IAA showed satisfactory drug profiles, and millimolar concentrations could be achieved in tumor tissue at non-toxic doses. HRP-expressing tumors showed a modest growth delay when treated with IAA compared with drug-vehicle controls. Treatment response could not be improved using different drug scheduling or drug vehicle, nor by combining HRP-directed gene therapy with fractionated radiotherapy.
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页码：420 / 428
页数：8
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