Characterization of a recombinant adenovirus vector encoding heat-inducible feline interleukin-12 for use in hyperthermia-induced gene-therapy.
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.
Siddiqui
Farzan
F
Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA. fsiddiq1@hfhs.org
Li
Chuan-Yuan
CY
Zhang
Xiuwu
X
Larue
Susan M
SM
Dewhirst
Mark W
MW
Ullrich
Robert L
RL
Avery
Paul R
PR
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002415:Cats; D002460:Cell Line; D004247:DNA / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012509:Sarcoma / Q000628:therapy; D013696:Temperature; D014162:Transfection; D019076:Transgenes / Q000235:genetics*
D004279:DNA, Viral; D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; D018664:Interleukin-12; D007371:Interferon-gamma; D004247:DNA