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

Int J Hyperthermia. 2006 Mar;22(2):117-34. doi: 10.1080/02656730500462309.

Abstract

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.

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Cats
  • Cell Line
  • DNA / genetics
  • DNA, Viral / genetics
  • Gene Expression Regulation / physiology
  • Genetic Therapy / methods*
  • Genetic Vectors / genetics*
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / physiology
  • Humans
  • Hyperthermia, Induced / methods*
  • Interferon-gamma / metabolism
  • Interleukin-12 / genetics*
  • Leukocytes, Mononuclear / metabolism
  • Promoter Regions, Genetic / genetics
  • Promoter Regions, Genetic / physiology
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Sarcoma / therapy
  • Temperature
  • Transfection
  • Transgenes / genetics*

Substances

  • DNA, Viral
  • HSP70 Heat-Shock Proteins
  • RNA, Messenger
  • Interleukin-12
  • Interferon-gamma
  • DNA