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Updated: Jun 28, 2026

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
08:19

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Translational strategies exploiting TNF-alpha that sensitize tumors to radiation therapy

H J Mauceri1, M A Beckett, H Liang

  • 1Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL, USA.

Cancer Gene Therapy
|November 1, 2008
PubMed

Insights

This study reveals that the tumor necrosis factor-alpha (TNF-alpha) therapy, Ad.Egr-TNF, combined with irradiation, effectively inhibits melanoma tumor growth by targeting tumor-associated endothelial cells. This highlights TNF-alpha signaling

Area of Science:

  • Oncology
  • Gene Therapy
  • Immunology

Background:

  • TNFerade (Ad.Egr-TNF) is an adenoviral vector expressing tumor necrosis factor-alpha (TNF-alpha).
  • It is in phase III trials for pancreatic cancer.
  • The role of TNF-alpha in radiosensitization is under investigation.

Purpose of the Study:

  • To investigate the mechanism of Ad.Egr-TNF-mediated radiosensitization in B16-F1 melanoma tumors.
  • To determine the role of TNF-alpha receptors in Ad.Egr-TNF's radiosensitizing effects.
  • To identify the primary cellular targets of Ad.Egr-TNF in tumor radiosensitization.

Main Methods:

  • Utilized B16-F1 melanoma tumor models in wild-type (C57BL/6) and TNF receptor-deficient mice (TNFR1,2-/- and TNFR1-/-).
  • Administered Ad.Egr-TNF combined with irradiation (IR).
  • Assessed tumor growth inhibition, tumor-associated endothelial cell apoptosis, and radiosensitivity in various genetic knockout models and with anti-TNF-alpha treatment.

Main Results:

  • Ad.Egr-TNF + IR inhibited tumor growth in wild-type mice but not in receptor-deficient mice.
  • Tumors resistant to TNF-alpha alone were sensitive to Ad.Egr-TNF + IR.
  • Increased tumor-associated endothelial cell apoptosis was observed in wild-type but not deficient mice.
  • Tumors in mice lacking TNF-alpha signaling components exhibited radiosensitivity.

Conclusions:

  • Tumor-associated endothelium is the primary target for Ad.Egr-TNF-induced radiosensitization.
  • TNF-alpha signaling plays a crucial role in mediating tumor radiosensitivity.
  • Ad.Egr-TNF represents a promising strategy for enhancing cancer radiotherapy.

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