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

Helena J. Mauceri, Nader N. Hanna, Jeffrey D. Wayne, Dennis E. Hallahan, Samuel Hellman, Ralph R. Weichselbaum*

*Corresponding author for this work

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

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) α(Ad. Egr-TNF) enhances the tumoricidal action of ionizing radiation in a human epidermoid carcinoma xenograft (SQ-20B). The dominant histopathological feature in tumorbearing 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 vital construct encoding TNF-α 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-α and X-irradiation occurs selectively within the tumor vessels.

Original languageEnglish (US)
Pages (from-to)4311-4314
Number of pages4
JournalCancer Research
Volume56
Issue number19
StatePublished - Oct 1 1996

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Mauceri, H. J., Hanna, N. N., Wayne, J. D., Hallahan, D. E., Hellman, S., & Weichselbaum, R. R. (1996). Tumor necrosis factor α (TNF-α) gene therapy targeted by ionizing radiation selectively damages tumor vasculature. Cancer Research, 56(19), 4311-4314.