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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. [ABSTRACT FROM AUTHOR]

Radioimmunotherapy (RIT) is a new and effective treatment modality in patients with non-Hodgkin's lymphoma. The monoclonal antibody (mAb) hLL2 (epratuzumab), a humanized mAb directed against the CD22 antigen, and which internalizes, can be labeled with various radionuclides. The biodistribution of hLL2 labeled with 131I, 186Re, 177Lu, and 88Y was studied in nude mice with subcutaneous human lymphoma xenografts in order to determine the most suitable of these four radionuclides for RIT with hLL2. Methods: Human Ramos lymphoma xenografts were transplanted in cyclophosphamide-pretreated athymic BALB/c mice. Four groups of mice were injected intravenously with 131I-, 186Re-, 88Y-, or 177Lu-labeled hLL2, respectively. To determine the nonspecific tumor uptake, two groups of mice received 88Y-labeled or 131I-labeled control antibody, cG250. The biodistribution of the radiolabel was determined 1, 3, and 7 days postinjection (p.i.). Results: Radiolabeled hLL2 had a higher tumor uptake than the nonspecific mAb at all time-points, irrespective of the radiolabel used. Tumor accretion of 88Y- and 177Lu-hLL2 was higher than tumor uptake of 131I- and 186Re-hLL2. Activity in the bone, represented by the femur without bone marrow, was higher for 177Lu- and 88Y-hLL2 than for 131I- and 186Re-hLL2 on day 7 p.i. Conclusion: The use of the residualizing radiolabels 88Y and 177Lu in combination with a mAb directed against an internalizing antigen resulted in higher uptake and better retention of the radiolabel in the tumor. [ABSTRACT FROM AUTHOR]