Abstract
Background: The anticancer role of tumor necrosis factor-alpha (TNF-α) has been limited by toxicity. These experiments evaluate blocking endogenous interferon-gamma (IFN-γ) activity to abrogate TNF-α toxicity.
Methods: C57Bl/6 mice bearing MCA 105 tumor were treated with TNF-α and anti-IFN-γ antibody (Ab) to evaluate the effect on the acute lethality of TNF-α and their efficacy as evaluated by tumor growth rate, tumor histology, and survival.
Results: Anti-IFN-γ Ab decreased TNF-α lethality. Anti-IFN-γ Ab alone increased tumor growth significantly more than did nonimmune IgG (p2<0.0001). Tumor-bearing mice that received nonimmune IgG and TNF-α had slower tumor growth (p2<0.02) and a trend toward improved survival (p=0.07) compared with saline-treated controls. Anti-IFN-γ Ab abrogated the antitumor effect of TNF-α, prevented acute tumor necrosis histologically, and resulted in tumor growth rate and host survival similar to that of controls. The findings in mice that received anti-IFN-γ Ab and high-dose TNF-α were comparable with those in mice that received a lower, equitoxic dose of TNF-α alone.
Conclusions: Blocking endogenous IFN-γ accelerates tumor growth in this model and partially abrogates the toxic and antitumor activity of exogenous TNF-α equally. This suggests that blocking endogenous IFN-γ activity is not a useful strategy for limiting TNF-α treatment toxicity.
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Doherty, G.M., Richard Alexander, H., Merino, M.J. et al. Role of endogenous interferon gamma in murine tumor growth and tumor necrosis factor alpha antitumor efficacy. Annals of Surgical Oncology 3, 198–203 (1996). https://doi.org/10.1007/BF02305801
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DOI: https://doi.org/10.1007/BF02305801