877 ANTI-IL10-R1 MONOCLONAL ANTIBODY ENHANCES BACILLUS CALMETTE-GUERIN (BCG) INDUCED TH1 AND ANTI-BLADDER CANCER IMMUNE RESPONSES IN VITRO AND IN VIVO

You have accessJournal of UrologyBladder Cancer: Basic Research II1 Apr 2012877 ANTI-IL10-R1 MONOCLONAL ANTIBODY ENHANCES BACILLUS CALMETTE-GUERIN (BCG) INDUCED TH1 AND ANTI-BLADDER CANCER IMMUNE RESPONSES IN VITRO AND IN VIVO Nathan A. Bockholt, Matthew J. Knudson, Jonathan R. Henning, Peter Weady, George J. Smith, Michael D. Eisenbraun, James D. Fraser, Michael A. O'Donnell, and Yi Luo Nathan A. BockholtNathan A. Bockholt Iowa City, IA More articles by this author , Matthew J. KnudsonMatthew J. Knudson Iowa City, IA More articles by this author , Jonathan R. HenningJonathan R. Henning Iowa City, IA More articles by this author , Peter WeadyPeter Weady San Diego, CA More articles by this author , George J. SmithGeorge J. Smith San Diego, CA More articles by this author , Michael D. EisenbraunMichael D. Eisenbraun San Diego, CA More articles by this author , James D. FraserJames D. Fraser San Diego, CA More articles by this author , Michael A. O'DonnellMichael A. O'Donnell Iowa City, IA More articles by this author , and Yi LuoYi Luo Iowa City, IA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.972AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Proper induction of Th1 immunity is required for effective BCG immunotherapy of bladder cancer. IL-10 down-regulates the Th1 response and is associated with BCG failure. We propose that blocking IL-10 receptor (IL-10R) can inhibit IL-10 signaling, thus enhancing BCG-induced antitumor response. METHODS Splenocytes were incubated with BCG alone or in combination with control IgG, anti-IL-10R1 mAb, or anti-IL-10 neutralizing mAb for 24 hours, followed by ELISA analysis of IFN-ω production. Bladder RNAs were extracted after intravesical (i.b.) BCG plus intraperitoneal (i.p.) control IgG or anti-IL-10R1 mAb and analyzed by qPCR. Urine was collected and analyzed by ELISA. Mice bearing luciferase-expressing MB49 orthotopic tumor were treated with i.b. BCG plus i.p. control IgG or anti-IL-10R1 mAb. Tumor response was assessed using bioluminescence imaging. RESULTS BCG plus anti-IL-10R1 mAb induced significantly higher IFN-ω than BCG plus anti-IL-10 neutralizing mAb (5.9-17.5 vs. 0.95-6.9 fold increases at 0.004-1 μg/ml). BCG plus anti-IL-10R1 mAb also induced substantially higher IFN-ω in both urine and bladder than BCG plus control IgG. Mice treated with PBS, BCG plus control IgG, or BCG plus anti-IL-10R1 mAb showed 0% tumor free with a 20% death rate, 20% tumor free with a 20% death rate, and 40% tumor free with a 0% death rate, respectively. CONCLUSIONS Anti-IL-10R1 mAb is more potent than anti-IL-10 neutralizing mAb for enhancing BCG-induced IFN-ω production in vitro. Anti-IL-10R1 mAb also enhances BCG-induced Th1 and antitumor immunity in vivo. This mAb could serve as an effective agent for treating bladder cancer when combined with BCG. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e357 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nathan A. Bockholt Iowa City, IA More articles by this author Matthew J. Knudson Iowa City, IA More articles by this author Jonathan R. Henning Iowa City, IA More articles by this author Peter Weady San Diego, CA More articles by this author George J. Smith San Diego, CA More articles by this author Michael D. Eisenbraun San Diego, CA More articles by this author James D. Fraser San Diego, CA More articles by this author Michael A. O'Donnell Iowa City, IA More articles by this author Yi Luo Iowa City, IA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...