Therapeutic effects of monoclonal antibody g250, interferons and tumor necrosis factor, in mice with renal‐cell carcinoma xenografts

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Abstract
Because renal‐cell carcinoma (RCC) is considered relatively resistant to radio‐and chemotherapy, RCC patients may benefit from new treatment modalities, e.g. immunotherapy. In vitro and in vivo studies suggest that combinations of cytokines such as interferon γ or interferon a (IFN‐γ, IFN‐α) and tumor necrosis factor a (TNF‐α) may act synergistically. In this study we tested whether a monoclonal antibody (MAb) G250, reactive with a RCC‐associated antigen, showed anti‐tumor effects in vivoin nude mice with established s.c. human RCC xenografts, and also whether this MAb could enhance the anti‐tumor effect of combinations of IFNs and TNF‐α. Treatment with combinations of IFN‐α/TNF‐α or IFN‐γ/TNF‐α, or with MAb G250 alone, resulted in a significant inhibition of tumor growth. Treatment with MAb G250, in combination with IFN‐γ/TNF‐α, did not result in an improve anti‐tumor effect as compared to that of either treatment alone. In contrast, MAb G250 combined with IFN‐α/TNF‐α resulted in a significantly enhanced anti‐tumor response. In one experiment, 3 out of 10 mice showed complete tumor regression, with no recurrence after 90 days. Large numbers of infiltrating macrophages were found surrounding viable and necrotic tumor tissue after treatment with G250 combined with IFN‐α/TNF‐α. These results suggest that combination therapy, consisting of IFN‐α, TNF‐α and MAbs, may have therapeutic value in the treatment of RCC.