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. 1995 Sep;40(5):315–321. doi: 10.1007/BF01519632

Potentiation of antitumor effects of tumor necrosis factor α and interferon γ by macrophage-colony-stimulating factor in a MmB16 melanoma model in mice

Witold Lasek 1,✉, Anna Wańkowicz 1, Katarzyna Kuc 1, Wojciech Feleszko 1, Jakub Golab 1, Adam Giermasz 1, Wiesŀaw Wiktor-J/cedrzejczak 2, Marek Jakóbisiak 1
PMCID: PMC11037724  PMID: 7600564

Abstract

The efficacy of systemic infusion of recombinant human macrophage-colony-stimulating factor (M-CSF) in combination with local treatment with human recombinant tumor necrosis factor (TNF) α and mouse recombinant interferon (IFN) γ was studied in vivo on a subclone of B16 melanoma (MmB16) in mice. Short-term intravenous administration of M-CSF at a dose of 106 units daily had no antitumor effect in vivo. Similarly, local treatment of tumor with TNFα (5 μg daily) did not produce any therapeutic effect. However, simultaneous administration of the same dose of TNFα with IFNγ (1000 units daily) resulted in a synergistic effects manifested by the retardation of tumor growth. Addition of systemic infusion of M-CSF to the local therapy with TNFα and IFNγ induced further augmentation of antitumor efficacy and delayed progression of MmB16 melanoma. The strengthened antitumor effect of combination therapy including M-CSF, TNFα and IFNγ was most probably due to the increased release of monocytes from the bone marrow, their recruitment into the site of tumor growth and subsequent local stimulation of their antitumor activity.

Key words: Tumor necrosis factor α, Interferon γ, Macrophage-colony-stimulating factor, Tumor immunotherapy

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