Interferons can upregulate the expression of the tumor associated antigen G250-MN/CA IX, a potential target for (radio)immunotherapy of renal cell carcinoma.
BACKGROUND
Interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) 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-alpha, and IFN-gamma 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-alpha or IFN-gamma, 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-gamma being the more potent agent. G250 expression could be upregulated four-fold. Interestingly, the effect of combining IFN-alpha and IFN-gamma 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-alpha and IFN-gamma. 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.
D000911:Antibodies, Monoclonal / Q000032:analysis / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000276:immunology / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D007700:Kinetics; D011485:Protein Binding / Q000276:immunology; D016499:Radioimmunotherapy; D011994:Recombinant Proteins; D013997:Time Factors; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D004338:Drug Combinations; C106533:G250 monoclonal antibody; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma; D007372:Interferons; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases