Interferons Can Upregulate the Expression of the Tumor Associated Antigen G250-MN/CA IX, a Potential Target for (Radio)Immunotherapy of Renal Cell Carcinoma

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Abstract
Background: Interleukin-2 (IL-2) and interferon-α (IFN-α) can induce therapeutic responses in a minority (5-25%) of patients with metastatic renal cell carcinoma (RCC). G250-MN/CA IX, a tumor-associated antigen expressed on the majority of clear cell RCCs, is a potential (radio)immunotherapeutic target for G250-antibody based (radio)immunotherapy. We investigated the effect of the biological response modifiers (BRMs) IL-2, IFN-α, and IFN-γ on the expression of the G250 antigen on RCC cells. Methods: In vitro, the expression of the G250 antigen was measured by flow cytometry (FCM) after culturing RCC cells in the presence of various concentrations of the BRMs. Additionally, the number of G250 epitopes per cell was determined quantitatively by Scatchard analysis. Results: Upregulation of G250 expression was observed on RCC cells cultured in the presence of IFN-α or IFN-γ, whereas the addition of IL-2 had no effect. For both IFNs a clear dose-response relation between G250 antigen expression and IFN dose was observed, with IFN-γ being the more potent agent. G250 expression could be upregulated four-fold. Interestingly, the effect of combining IFN-α and IFN-γ revealed a more pronounced upregulation of G250 expression than either one of the IFNs alone. Conclusions: On the basis of in vitro experiments, G250 expression can be upregulated by IFN-α and IFN-γ. In vivo studies are warranted to investigate whether due to IFN treatment increased G250 expression occurs, and whether increased G250 expression can enhance the therapeutic efficacy of G250-antibody based (radio)immunotherapy.