The Immunocytokine F8-IL2 Improves the Therapeutic Performance of Sunitinib in a Mouse Model of Renal Cell Carcinoma

No AccessJournal of UrologyInvestigative Urology1 Dec 2010The Immunocytokine F8-IL2 Improves the Therapeutic Performance of Sunitinib in a Mouse Model of Renal Cell Carcinoma Katharina Frey, Christoph Schliemann, Kathrin Schwager, Raffaella Giavazzi, Manfred Johannsen, and Dario Neri Katharina FreyKatharina Frey Department of Chemistry and Applied Biosciences, Eidgenössische Technische Hochschule Zürich, Zürich, Switzerland , Christoph SchliemannChristoph Schliemann Department of Chemistry and Applied Biosciences, Eidgenössische Technische Hochschule Zürich, Zürich, Switzerland Department of Medicine A-Hematology, Oncology and Pneumology, University Hospital Münster, Münster, Germany , Kathrin SchwagerKathrin Schwager Philochem AG, Eidgenössische Technische Hochschule Zürich, Zürich, Switzerland , Raffaella GiavazziRaffaella Giavazzi Department of Oncology, Mario Negri Institute for Pharmacological Research, Via Giuseppe La Masa 19, 20156 Milano, Italy , Manfred JohannsenManfred Johannsen Department of Urology, Charité Berlin, Berlin, Germany , and Dario NeriDario Neri Department of Chemistry and Applied Biosciences, Eidgenössische Technische Hochschule Zürich, Zürich, Switzerland View All Author Informationhttps://doi.org/10.1016/j.juro.2010.07.030AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We investigated the therapeutic action of F8-IL2, a fusion protein consisting of the F8 antibody specific to the alternatively spliced extradomain-A of fibronectin, in diabody format and of human interleukin-2 in the Caki-1 (ATCC®) model of human renal cell carcinoma grafted subcutaneously in nude mice. Materials and Methods: F8-IL2 was cloned, expressed in CHO cells and purified to homogeneity. This immunocytokine was administered alone or combined with 3 standard drugs commonly used as therapy for kidney cancer, including sunitinib, sorafenib and interferon-α, in 2 sets of doses and treatment schedules. Results: Neither F8-IL2 nor any other therapeutic agent cured tumor bearing mice when used as a single agent. The best therapeutic results were observed for the combination of sunitinib with F8-IL2 in a continuous administration schedule, which yielded a 28% cure rate and substantial tumor growth retardation. Conclusions: Considering that recombinant interleukin-2 based immunocytokines are now being investigated in several clinical trials in patients with cancer alone or combined with chemotherapy our preclinical results provide a motivation to study F8-IL2 combined with sunitinib in clinical trials in patients with kidney cancer. References 1 : Renal cell carcinoma. 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Fiebig, Freiburg, Germany, provided RXF393.MetricsAuthor Information Katharina Frey Department of Chemistry and Applied Biosciences, Eidgenössische Technische Hochschule Zürich, Zürich, Switzerland More articles by this author Christoph Schliemann Department of Chemistry and Applied Biosciences, Eidgenössische Technische Hochschule Zürich, Zürich, Switzerland Department of Medicine A-Hematology, Oncology and Pneumology, University Hospital Münster, Münster, Germany More articles by this author Kathrin Schwager Philochem AG, Eidgenössische Technische Hochschule Zürich, Zürich, Switzerland More articles by this author Raffaella Giavazzi Department of Oncology, Mario Negri Institute for Pharmacological Research, Via Giuseppe La Masa 19, 20156 Milano, Italy More articles by this author Manfred Johannsen Department of Urology, Charité Berlin, Berlin, Germany Financial interest and/or other relationship with Pfizer Germany, Bayer, Novartis Germany, Wyeth Germany, Roche Germany and GlaxoSmithKline. More articles by this author Dario Neri Department of Chemistry and Applied Biosciences, Eidgenössische Technische Hochschule Zürich, Zürich, Switzerland Financial interest and/or other relationship with Philogen. More articles by this author Expand All Advertisement PDF DownloadLoading ...