MP35-06 EFFECTS OF DENDRITIC CELL-BASED AD-GM∙CAIX VACCINE AS MONOTHERAPY OR IN COMBINATION WITH SUNITINIB IN AN IMMUNOCOMPETENT MOUSE MODEL OF METASTATIC RENAL CELL CARCINOMA

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research III1 Apr 2014MP35-06 EFFECTS OF DENDRITIC CELL-BASED AD-GM∙CAIX VACCINE AS MONOTHERAPY OR IN COMBINATION WITH SUNITINIB IN AN IMMUNOCOMPETENT MOUSE MODEL OF METASTATIC RENAL CELL CARCINOMA Edward N. Rampersaud, Jonathan W. Said, Adrian Bot, Frédéric D. Birkhäuser, Nils Kroeger, Gang Zeng, Fairooz F. Kabbinavar, Antoni Ribas, Allan J. Pantuck, Arie S. Belldegrun, and Joseph Riss Edward N. RampersaudEdward N. Rampersaud More articles by this author , Jonathan W. SaidJonathan W. Said More articles by this author , Adrian BotAdrian Bot More articles by this author , Frédéric D. BirkhäuserFrédéric D. Birkhäuser More articles by this author , Nils KroegerNils Kroeger More articles by this author , Gang ZengGang Zeng More articles by this author , Fairooz F. KabbinavarFairooz F. Kabbinavar More articles by this author , Antoni RibasAntoni Ribas More articles by this author , Allan J. PantuckAllan J. Pantuck More articles by this author , Arie S. BelldegrunArie S. Belldegrun More articles by this author , and Joseph RissJoseph Riss More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1049AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Metastatic clear cell renal cell carcinoma (ccRCC) poses a therapeutic challenge because of its resistance to conventional treatment. This study evaluates the efficacy of a novel dendritic cell based vaccine targeting human carbonic anhydrase IX (hCAIX; DC-Ad-GM∙CAIX) in treating metastatic ccRCC as monotherapy and in combination with sunitinib. METHODS Balb/c mice were orthotopically-transplanted with syngeneic RCC-hCAIXpositive (NPR-IX) tumor cells, immunized, and/or treated with sunitinib at low-dose (5mg/kg/d), high-dose (40mg/kg/d) or left untreated. At termination, primary tumor size (weight), lung metastatic burden (number of foci and their size), hCAIX tumor expression and immune-markers were evaluated and compared. RESULTS Mono-immunotherapy with DC-Ad-GM∙CAIX vaccine suppressed metastatic tumor growth: the total number of metastatic heterotypic foci following vaccination decreased 2.5 fold compared with untreated mice (P<0.05). When counting only the hCAIX positive metastatic tumor cells, the decrease in the metastatic tumor burden compared to untreated mice was even more pronounced (>10 fold). Vaccination alone resulted in reduced primary tumor burden of RCC-hCAIXpositive cells to <25% of the tumor cell population, with the remaining cells lacking hCAIX expression (hCAIXnegative); there was no significant overall primary tumor reduction compared to untreated mice. In contrast, sunitinib, whether given as high-dose monotherapy or in combination with the vaccine, inhibited the primary orthotopic tumors, achieving 35% (P=0.0001) and 51% (P=1.7e-7) tumor reduction, respectively. However, sunitinib monotherapy was less effective in reducing the metastatic tumor burden compared with the vaccine. In fact, simultaneous administration of vaccine and sunitinib increased the metastatic tumor burden in heterotypic tumors composed also of hCAIXnegative cells. CONCLUSIONS This study demonstrates: (i) DC-Ad-GM∙CAIX vaccine is effective in clearing both primary and metastatic tumor cells expressing hCAIX, (ii) Antigen editing with loss of hCAIX is an important immune escape mechanism, and (iii) Sunitinib may be detrimental when given in combination with the vaccine. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e372 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Edward N. Rampersaud More articles by this author Jonathan W. Said More articles by this author Adrian Bot More articles by this author Frédéric D. Birkhäuser More articles by this author Nils Kroeger More articles by this author Gang Zeng More articles by this author Fairooz F. Kabbinavar More articles by this author Antoni Ribas More articles by this author Allan J. Pantuck More articles by this author Arie S. Belldegrun More articles by this author Joseph Riss More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...