Regression of Human Breast Cancer Xenografts in Response to Intralesional Treatment with Interferons α and γ Potentiated by Tumor Necrosis Factor

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Abstract
The potentiating effects of human recombinant tumor necrosis factor-α (rTNF-α) on the antitumor actions of recombinant interferon-γ (rIFN-γ) and of natural interferons α and γ combined (nIFN-α/nIFN-γ) were studied on human breast cancer xenografts growing bilaterally in nude mice. The cytokines were injected singly or in combination in one of the two tumors of each mouse to study local effects while the opposite tumor was left undisturbed to evaluate systemic effects. The tumors received 20 intralesional injections (four cycles of 5 daily injections each). In injected tumors the best results were obtained with nIFN-α/nIFN-γ supplemented with rTNF-α. The responses were dose dependent, resulting in complete regressions of 9 of 9 tumors with rTNF-α used at the dose of 5 μg per injection, of 6 of 8 tumors at the dose of 2.5 μg, and of 4 of 8 tumors at the dose of 0.5 μg. Mostly mild to moderate partial responses were seen in the other groups. The systemic effects on the contralateral tumors were significantly less than the local effects on the corresponding tumors. Histologically, responding tumors showed reactive fibrosis and inflammatory cell infiltration. No vascular alterations were seen, presumably because of the immunodeficiency of nude mice. It was concluded that the potentiation of the antitumor actions of IFNs by rTNF-α was effective at the local but not at the systemic level.