Tumor necrosis factor alpha (TNF-alpha) gene therapy targeted by ionizing radiation selectively damages tumor vasculature

Cancer Res. 1996 Oct 1;56(19):4311-4.


Intratumoral injection of an adenoviral vector containing radiation-inducible DNA sequences of the Egr-1 promoter linked to a cDNA encoding tumor necrosis factor (TNF) alpha (Ad.Egr-TNF) enhances the tumoricidal action of ionizing radiation in a human epidermoid carcinoma xenograft (SQ-20B). The dominant histopathological feature in tumor-bearing animals treated with Ad.Egr-TNF and irradiation is extensive intratumoral vascular thrombosis and tumor necrosis. Thrombosis and necrosis are not observed in animals treated with either the viral construct encoding TNF-alpha or radiation and did not occur in irradiated normal tissues adjacent to tumor in animals injected with Ad.Egr-TNF. To determine if the occlusive effects of Ad.Egr-TNF and X-irradiation were specific for tumor vessels, non-tumor-bearing mice were irradiated after receiving i.m. injection of Ad.Egr-TNF at viral titers 20-100 times greater than titers injected intratumorally. No vascular thrombosis was observed in the treated normal tissues. Combined Ad.Egr-TNF and radiation produced occlusion of tumor microvessels without significant normal tissue damage. Taken together, these data suggest that the interaction between radiation inducible TNF-alpha and X-irradiation occurs selectively within the tumor vessels.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / blood supply
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Female
  • Gene Expression Regulation / radiation effects*
  • Genetic Therapy*
  • Genetic Vectors / genetics
  • Genetic Vectors / radiation effects
  • Humans
  • Mice
  • Mice, Nude
  • Necrosis
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / genetics*
  • Recombinant Fusion Proteins / biosynthesis
  • Thrombosis / etiology
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics*


  • Recombinant Fusion Proteins
  • Tumor Necrosis Factor-alpha