Characterization of a recombinant adenovirus vector encoding heat-inducible feline interleukin-12 for use in hyperthermia-induced gene-therapy

被引:13
作者
Siddiqui, Farzan [1 ]
Li, Chuan-Yuan
Zhang, Xiuwu
Larue, Susan M.
Dewhirst, Mark W.
Ullrich, Robert L.
Avery, Paul R.
机构
[1] Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA
[2] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA
[3] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA
关键词
hyperthermia; adenovirus; interleukin-12; heat shock promoter;
D O I
10.1080/02656730500462309
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Interleukin-12 (IL-12) is a pro-inflammatory cytokine that has shown great promise as a therapeutic agent in experimental models of infectious disease and cancer. However, it is also a highly toxic molecule and for that reason has not been accepted readily into the clinic. A replication-deficient adenoviral vector was designed to deliver the feline interleukin-12 gene into tumour cells. The interleukin-12 gene has been placed under control of a heat inducible promoter, human heat shock promoter 70b, with the intent of spatially and temporally controlling the expression of IL-12, thus limiting its toxicity. In vitro, the transfection efficiency of the adenoviral vector, the effect of multiplicity of infection and the production of biologically active feline IL-12 were studied in the infected cells in response to a range of temperatures. This adenoviral vector will be a useful tool to examine the effects of intra-tumoural IL-12 delivery in a spontaneously occurring feline soft tissue sarcoma model.
引用
收藏
页码:117 / 134
页数:18
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